The recent introduction of foot-and-mouth disease virus serotype O (O/EA-2 topotype) in Southern Africa region has changed virus dynamics and the FMD vaccine requirements. This study describes an assessment of the heterologous antibody responses induced by O Manisa vaccine (three PD50/dose) against a representative O/EA-2 virus collected from an FMD outbreak in Zambia. Commercial and subsistence cattle herds were monitored following vaccination, where the benefits of employing a double vaccination schedule were compared to single-dose vaccination. Testing using virus neutralisation showed cattle that received two vaccine doses had a mean reciprocal log virus neutralisation titre of 2.02 (standard error [SE] = 0.16, n = 9) for commercial herds and 1.65 (SE = 0.17, n = 5) for subsistence herds , 56 days after first vaccination (dpv). Significantly lower mean titres were observed for single-dosed commercial herds (0.90, SE = 0.08, n = 9) and subsistence herds (1.15, SE = 0.18, n = 3), 56 dpv. Comparison of these results and those generated by solid-phase competitive ELISA by cohen’s kappa coefficient observed a statistically significant (ρ = 0.598 for 1:10 dilution, and ρ = 0.562 for 1:30 dilution of SPCE % inhibition results, p < 0.001 for both dilutions) positive correlation.

As of the end of 2022, despite the disruptions caused by the COVID-19 pandemic, the global HIV epidemic persists, with 39 million individuals living with the virus and 1.3 million new infections reported in that year. Opportunistic infections associated with AIDS claimed the lives of over 630,000 people in 2022, contributing to a cumulative death toll exceeding 40.4 million since the disease's emergence in 1981. Although advances in HIV diagnosis and antiretroviral therapy have transformed the disease into a manageable chronic condition, issues like drug resistance, low compliance, and high treatment costs persist. Until a vaccine becomes available, a comprehensive approach involving prevention and therapy is essential, particularly for high-risk populations. Research shows that prevention strategies are more cost-effective than treatment. The development of antiretroviral drugs has also spurred the creation of antivirals for other infections. The emergence of COVID-19 vaccines has opened new avenues for HIV vaccine development, as lessons from vaccine platform technologies like mRNA, viral vectors, and protein subunits can be applied to HIV. This review explores the most promising prophylactic and therapeutic HIV vaccine trials, emphasizing the need for a multi-pronged approach combining vaccines with non-vaccine strategies. Though significant progress is anticipated, the road to a viable HIV vaccine remains long, especially for high-risk populations, such as medical workers, blood transfusion recipients, and drug users. The combinatorial approach, capitalizing on various aspects of immunity, may hold the key to defeating HIV in the future.

Background Healthcare workers (HCWs) have suffered considerable morbidity and mortality during the COVID-19 pandemic. Few data on COVID-19 vaccine effectiveness (VE) are available from middle-income countries in Europe. We evaluated primary series COVID-19 VE against laboratory-confirmed COVID-19 among HCWs in Georgia. Methods HCWs in six hospitals in Georgia were invited to enroll in a prospective cohort study conducted during March 19–December 5, 2021. Participants completed weekly symptom questionnaires. Symptomatic HCWs were tested by RT-PCR and/or rapid antigen test (RAT), and participants were routinely tested for SARS-CoV-2 by RT-PCR or RAT, regardless of symptoms. Serology was collected at enrolment, and quarterly thereafter, and tested by electrochemiluminescence immunoassay for SARS-CoV-2 antibodies. We defined primary series vaccination as two doses of COVID-19 vaccine received ≥14 days before symptom onset. We estimated VE as (1-hazard ratio)*100 using a Cox proportional hazards model with vaccination status as a time-varying covariate. Estimates were adjusted by potential confounders that changed the VE estimate by more than 5%, according to the change-in-estimate approach. Results Overall, 1561/3849 (41%) eligible HCWs enrolled and were included in the analysis. The median age was 40 (IQR: 30-53), 1318 (84%) were female, and 1003 (64%) had laboratory evidence of prior SARS-Cov-2 infection. At enrolment, 1300 (83%) were unvaccinated; By study end, 1082 (62%) had completed a primary vaccine series (69% BNT162b2 (Pfizer-BioNTech); 22% BBIBP-CorV (Sinopharm); 9% other). During the study period, 191(12%) participants had a new PCR- or RAT-confirmed symptomatic SARS-CoV-2 infection. VEa gainst PCR- or RAT- confirmed symptomatic SARS-CoV-2 infection was 58 (95%CI: 41; 70) for all primary series vaccinations, 68% (95%CI: 51; 79) for BNT162b2, and 40% (95%CI: 1; 64) for BBIBP-CorV vaccines. Among previously infected HCWs, VE was 58% (95%CI: 11; 80). VE against medically attended COVID-19 was 52% (95%CI: 28; 68), and VE against hospitalization was 69% (95% CI: 36; 85). During the period of predominant Delta variant circulation (July-December 2021), VE against symptomatic COVID-19 was 52% (95%CI: 30; 66). Conclusions Primary series vaccination with BNT162b2 and BBIBP-CorV was effective at preventing COVID-19 among HCWs, most of whom had previous infection, during a period of mainly Delta circulation. Our results support the utility of COVID-19 primary vaccine series, and the importance of increasing coverage, even among previously infected individuals.

The analysis reported here is unique in that it is the first study of the original data from the Pfizer/BioNTech BNT162b2 mRNA vaccine clinical trial (CA4591001) to be carried out by a group unaffiliated with the trial sponsor. Our study is a forensic analysis of the 38 trial subjects who died between July 27, 2020, the start of Phase 2/3 of the clinical trial, and March 13, 2021, the data end date of their 6-Month Interim Report. Phase 2/3 of the trial involved 44,060 subjects who were equally distributed into two groups and received Dose 1 of either the BNT162b2 mRNA vaccinated or the Placebo control (0.9% normal saline). At Week 20, when the BNT162b2 mRNA vaccine received Emergency Use Authorization from the U.S. FDA, subjects in the placebo arm were given the option to be BNT162b2 vaccinated. All but a few accepted. Surprisingly, a comparison of the number of subject deaths per week during the 33 Weeks of this study found no significant difference between the number of deaths in the vaccinated versus placebo arms for the first 20 weeks of the trial, the placebo-controlled portion of the trial. After Week 20, as subjects in the Placebo were unblinded and vaccinated, deaths among this still unvaccinated cohort of this group slowed and eventually plateaued. Deaths in the BNT162b2 vaccinated subjects continued at the same rate. Our analysis revealed inconsistencies between the subject data listed in the 6-Month Interim Report and publications authored by Pfizer/BioNTech trial site administrators. Most importantly, we found evidence of an over 3.7-fold increase in number of deaths due to cardiovascular events in BNT162b2 vaccinated subjects compared to Placebo controls. This significant adverse event signal was not reported by Pfizer/BioNTech. Potential sources of these data inconsistencies are identified.

Delineating the epidemic of vaccine injury from the coterminous condition long covid is a challenging prospect, but one with many implications not just for treatment, but also has important legal considerations for settlements of vaccine injury. The shared etiological factor of the spike protein in both vaccine injury and long covid make differentiation difficult, and while treatment is largely similar between vaccine injury and long covid, there are important distinctions. Furthermore, diagnostics are important for monitoring treatment progress and assessing the extent of subclinical vaccine injury in population having received a covid-19 vaccine. The development of rigorous diagnostics is an important step towards the recognition of both long covid and vaccine injury, as those suffering these conditions have faced immense challenges in having their conditions recognized, treated, and compensated by insurance companies or national health services.

Background: To our knowledge, the sudden onset of symptomatic pulmonary hypertension after COVID-19 vaccination has not been described. Both cases presented here resulted in functional limitations and likely permanent organ damage. Case Summary: We report two cases of acute onset pulmonary hypertension in previously healthy adult males within three weeks of receiving the second dose of the Pfizer (BNT162b2) mRNA COVID-19 vaccine from different lots. Both patients experienced the sudden onset of severe fatigue and dyspnea on exertion with negative COVID-19 PCR testing. The diagnosis was made by serial transthoracic echocardiography in the first case and by both transthoracic echocardiography and right heart catheterization in the second. Discussion: Pulmonary hypertension is a serious disease characterized by damage to lung vasculature and restricted blood flow through narrowed arteries from the right to left heart. The onset of symptoms is typically insidious, progressive and incurable, leading to right heart failure and premature death. The World Health Organization (WHO) classifies pulmonary hypertension into 5 categories and recently re-defined as a resting mean pulmonary artery pressure greater than 20 mmHg. Sudden onset pulmonary hypertension would only be expected in the settings of surgical pneumonectomy or massive pulmonary emboli with compromise of at least 50% of the lung vasculature.

Traditional vaccines are produced by using weakened or inactivated forms of disease-causing pathogens to produce the target antigen they are designed to protect against. Messenger RNA vaccines are a class of vaccines that employ a minute segment of genetic material, known as messenger RNA (mRNA), which contains directives for the cells in the body to generate a particular protein. This genetic material is synthesized in the laboratory and packaged into a lipid nanoparticle, which protects and helps it enter cells for further protein synthesis. During vaccination with mRNA vaccine, the lipid nanoparticles containing the mRNA are injected into the muscle of vaccinees. Once inside the cells, the mRNA instructs the cells to produce a protein which is then displayed on the surface of the cell, triggering an immune response. During this, the immune system recognizes the displayed protein as foreign and mounts a defense by producing antibodies and activating immune cells to target and eliminate the protein. Furthermore, these immune responses generate a memory cell, facilitating the immune system to promptly react in case of encountering the authentic pathogen as an infection in the future. The mRNA vaccines are flexible and the sequence can be easily synthesized in the lab based on the genetic information of the target pathogen. Additionally, mRNA vaccines can be developed for new strains or variants of the target disease easily. This was particularly evident during the COVID-19 pandemic, where mRNA vaccines like the Pfizer-BioNTech and Moderna vaccines were developed and authorized for emergency use within a year. But currently, available mRNA vaccines require extensive cold chain, antigen delivery, potential immune response variability optimization, and sophisticated manufacturing process. The efforts to explore next-generation mRNA vaccine development are aimed to further improve the effectiveness, stability, and delivery methods. One focus of research has been to enhance the stability of mRNA vaccines, particularly temperature sensitivity which makes storage and distribution easier, particularly in regions with limited access to cold chain infrastructure. Self-amplifying mRNA vaccines, on the other hand, are designed to generate multiple copies of the mRNA within cells which potentially leads to a higher production of the target protein, resulting in a stronger immune response. Additionally, studies are exploring new delivery systems to improve the target and efficiency of mRNA vaccines using specialized nanoparticles and liposomes to specifically deliver mRNA to certain cell types or immune cells. Another area of interest is the development of combination vaccines, where multiple mRNA sequences are included in a single vaccine protecting against multiple diseases targeting strains or variants of a particular pathogen simultaneously. While current mRNA vaccines are administered via intramuscular injection, studies are underway to deliver directly into the skin offering enhanced immune response and the ability to use smaller vaccine doses.

Abstract Congenital rubella syndrome is a constellation of birth defects that can have devastating consequences, impacting approximately 100,000 births worldwide each year. The incidence is much lower in countries that routinely vaccinate their population. In the US, postnatal immunization of susceptible women is an important epidemiological strategy for the prevention of rubella. However, concerns that co-administration of Rubella vaccine with other immunoglobins (i.e., Rhogam) could comprise vaccine efficacy has produced warnings that can delay the administration of Rubella vaccination postpartum, leaving women susceptible in a subsequent pregnancy. We aimed to address whether co-administration of Rubella vaccine and Rhogam decreased antibody responses as compared to those receiving only Rubella vaccination. This retrospective cohort study utilized clinical data from 80 subjects who received Rubella vaccine and Rhogam after delivery and 43 subjects received Rubella vaccine alone. Maternal demographics, pregnancy complications and rubella status at the start of a subsequent pregnancy were recorded for analysis. Overall, the two cohorts had similar baseline characteristics; however, lower parity was noted in the participants having both Rubella vaccination and Rhogam. Based on maternal antibody IgG index for rubella during the next pregnancy, we observed that 88% of the Rhogam + Rubella vaccine group had positive titers, which was not significantly different than the 81% in the Rubella vaccine only cohort (p=0.36). In conclusion, no differences in the rubella immunity status in a subsequent pregnancy were observed in those mothers administered both Rubella vaccine and Rhogam concurrently. Given these findings, warnings against co-administration of Rubella vaccine in combination with other immunoglobulins should be discontinued.

Vaccine hesitancy remains a public health challenge. It has been argued that the sources of vaccine-related information may serve as important condiments to one’s decision to be vaccinated. However, little empirical attention is given to the subject. We contribute to this debate by assessing the level of COVID-19 vaccine hesitancy and the role of information explaining hesitancy, using the Nelson Mandela Bay Municipality of South Africa as a case study. Findings confirm high level of vaccine hesitancy, representing 78.8 percent of the respondents (which is above the national level of 41%). Furthermore, findings reveal that vaccination decisions are influenced by family, which is the most trusted among all institutions in the society, especially on sensitive matters and those shrouded by myths and misinformation. Additionally, the majority trusts health care workers and mass media as sources of health-related and general information; however, the use of popular personalities to convey health information is not supported. The findings reveal key socio-demographic and institutional drivers of COVD-9 vaccine hesitancy, such as age, inadequate information on the vaccine, trust issues, conspiracy beliefs, vaccine-related factors, and perceived side effects associated with the vaccine. Recommendations based on the findings are provided.

The phenomenon of vaccine hesitancy is a growing threat to public health with far-reaching implications. The widening gap between the vaccinated and the proportion needed for herd immunity raises two critical research questions that are of interest to practitioners, researchers, and policymakers: (1) What determines one’s decision to be vaccinated? and (2) What is the implication of COVID-19 vaccine hesitancy on economic recovery? In this study, we use empirical data in the context of South Africa to investigate factors affecting COVID-19 vaccine hesitancy and their implications for economic recovery. Findings reveal key socio-demographic and institutional drivers of COVD-9 vaccine hesitancy, which include age (the youth are more hesitant), inadequate information on the vaccine (those who perceive they have adequate information are vaccinated), trust issues in government institutions, conspiracy beliefs, vaccine-related factors, and perceived side effects associated with the vaccine. Additionally, an individual’s decision to remain hesitant about COVID-19 vaccination has implications for businesses and the economy by limiting movement and trade, increasing unemployment, and causing a resurgence of new variants. Based on the findings, action plans such as information dissemination, convenience vaccination centers, consistency communications, and targeted campaign strategies are recommended for improving vaccine intakes and a positive economic recovery.

Introduction. Covid-19 faced the world with serious health and socioeconomic issues. At the very beginning of the pandemics, the vaccine was considered by health authorities and the medical community the only way to curb the spread of the virus. One of the measures that have been proposed to increase vaccinations was the mandatory policy. The purpose of this study was to compare determinants of voluntary and mandatory vaccination among students of Albanian University. Methodology: This cross-sectional study by means of an online survey, was conducted among students enrolled in the private University “Albanian University”, Tirana, Albania during the last week of winter semester 7-14 Feb 2022. Results: 878 students participated in this study, among them 612 (69.7%) were females, 266 (30%) were males. 506 (57%) of the participants were enrolled in Medical Sciences (MS), 372(42.3%) were Non-Medical Science (Non-MS) group. 773 (88%) was vaccinated against Covid-19, 105 (11.8%) were not vaccinated. 466 (53%) reported voluntary vaccination, 412 (46.9%) reported mandatory vaccination. Among students that vaccinated voluntary 266 (57%) were from MS group, 200(42.9%) from Non-MS group. 237(57.5%) of students in mandatory vaccination group were from MS group, 175 (42.4%) from Non-MS. Conlusion. Vaccine safety and efficacy were hindering factors of vaccination. Also, based on the results of this study, the students felt encouraged to vaccinate by the academic staff. This clearly demonstrates that the staff does not lack the skills to enhance stu-dents' knowledge about the risk of infectious diseases and the importance of vaccination. Therefore, to influence as much as possible students’ attitude toward vaccination, comprehensive educational programs including modification of existing curricula should be considered.

Background Several vaccines have been approved for prevention of the coronavirus disease discovered on 31st December in Wuhan, China. Pakistan procured vaccines from various countries. However, the lack of knowledge and reluctance of the general population to embrace the use of the vaccines are considered to be the major determinants of the slow vaccination rate. Hence, it is necessary to evaluate the willingness of the general population about their perception of the COVID-19 vaccination. Methods A cross sectional survey based on a self-structured questionnaire comprising 18 questions was conducted (from April 21-June 21) on 400 Pakistani participants to evaluate their knowledge, attitude and perception towards the COVID-19 vaccination. Chi-square independent t-test and one-way Anova including a multiple step wise linear regression were used to draw conclusions about the results. P< 0.05 was considered significant. Results A total of 400 participants responded in the KAP survey of which 46.5% were female and 53.5% were male. The mean age of participants was 36.08 years. This survey showed a poor knowledge (50.5%), a fair attitude (75.1%) and a poor perception (58.1%) towards the COVID-19 vaccination. Higher mean knowledge and attitude scores was reported in the age group 21-40, females and unmarried urban citizens. Regression analysis showed that age, education, residence and employment status influenced the knowledge and perception score to a considerable extent. Conclusions The findings reflect an inadequate knowledge and perception on the one hand but a better attitude towards the COVID-19 vaccination. This KAP survey will help in better understanding the opinion of the general population towards vaccination and will be useful for policy makers and health care authorities aiming to increase the vaccination rate.

Rabies is a life-threatening and vaccine-preventable infectious disease and is triggered by an RNA virus, part of the Rhabdoviridae family, Lyssavirus genus. It is transmitted from infected saliva due to biting, but also from contact with infected blood or organs from rabid animals to humans. Children are at high risk due to their inability to defend themselves from infected animals and most deaths occur with a particularly high incidence in this category (under the age of 15 years). Postexposure prophylaxis (PEP) is standard and life-saving if given early after exposure. We are reporting the case of a ten-year-old female child, who was bitten by an unvaccinated cat ten days before admission to the Paediatric Intensive Care Unit at National Institute for Infectious Diseases „Prof. Dr Matei Bals”, Bucharest. The child had category III cat bites and did not receive PEP. Suggestive clinical manifestations such as an altered general state, psychomotor agitation, auditory and visual hallucinations, and hypersomnia followed by aerophobia and hydrophobia were present. Despite the maximal treatment introduced from early admission (Human Rabies Immunoglobulin, anti-rabies vaccination, orotracheal intubation plus mechanical ventilation, vital functions’ support, parenteral feeding, symptomatic drugs) the evolution of the patient was unfavourable, namely death two months after admission. The diagnosis was established in both pre-mortem by identifying the rabies virus in the cerebrospinal fluid based on reverse transcription-polymerase chain reaction (RT-PCR) and post-mortem by a histopathological examination (which reveals the presence of Babes-Negri bodies in the hippocampus). The objective is to understand the mechanism of infection and mortality from rabies virus in children. Conclusion: The most effective prevention methods are early administration of specific prophylaxis (immunoglobulin and vaccination) and, most importantly, early elimination of animal rabies outbreaks, while rapid diagnosis is helpful in the management of human rabies in humans. The rate of human exposure may be significantly decreased by controlling rabies through pet immunization programs.

Background: This study describes the attitudes and practices of Brazilian adults regarding the mandatory vaccination for COVID-19 and the hesitancy to children´s vaccination. Methods: The participants answered an online questionnaire disseminated on social networks. An adaptation of the SAGE-WG questionnaire was used to measure the children's vaccination hesitancy. Results: Among 1,007 participants, 677 (67.4%) believed that vaccination for COVID-19 among adults should be mandatory. Just over half of the participants (51.5%) believe that parents and guardians should be free to decide whether their children should be vaccinated against COVID-19, and 9.1% were unsure about this. Younger, non-religious people who have higher self-perceptions of risk for COVID-19, and who evaluate the federal government's performance in combating the disease as bad or very bad, have a higher agreement with mandatory vaccination, a lower agreement that parents and guardians should be free to vaccinate their children, and lower child vaccination hesitancy scores. Conclusion: In Brazil, mandatory COVID-19 vaccination for adults is far from a consensus, and an expressive part of the population believes that parents and guardians should be free to choose whether or not to vaccinate their children. These perceptions and vaccine hesitancy for children are associated with religious and political inclinations.

Introduction: Studies conducted in real-life scenarios on vaccine protection against COVID-19 constitute an important global priority, but one that is currently mostly neglected in low- and middle-income countries such as Angola. Here, we analyze for the first-time vaccine protection against COVID-19 in a real-life scenario after 6 months of implementing a multi-vaccination plan in Angola, providing estimation of odds ratios in vaccinated individuals and vaccine efficacy against infection by SARS-CoV-2 in a period that coincided with the identification of the Omicron variant in the country. Methods: We used a negative test case-control design to assess the effectiveness of vaccination against confirmed SARS-CoV-2 infection. A total of 4.232 vaccinated and unvaccinated individuals with the result of a rapid antigen diagnostic test against SARS-CoV-2 performed from December 27 to 28, 2021 were included in the study. Data were extracted from the Digital Vaccination Record Platform (Rediv) of the Ministry of Health of Angola. All ethical procedures related to the authorization necessary to carry out the study were followed. Statistical analyzes were performed using version 7.5.2.0 of CDC's Epi Info. Frequency distributions and measures of central tendency were used to characterize the study universe. The general and sex-adjusted and age-adjusted odds ratios, were evaluated by comparing the chances of vaccination between cases and controls, and their associated 95% CI, which were calculated using the Mantel-Haenszel stratification method. The risk classification of Axel Kroeger, Piscoya and Alarcon was used to interpret the odds ratio. The Breslow-Day statistic was used to assess the homogeneity of the odds ratios. Vaccine efficacy was calculated using the odds ratio applying the accepted statistical vaccine efficacy formula:(1 − odds ratio) × 100. For all estimates, a P value < 0.05 was considered statistically significant. Results: The population consisted of 63.63% male and 36.37% female. The mean age was 36 years with a standard deviation of 13. 83. Regarding vaccination status, 83.27% of individuals were vaccinated and 16.73% were unvaccinated, with 21.81% positive and 78.19% negative for SARS -CoV-2. The odds of SARS-CoV-2 infection were 0.85 (95% CI 0.70 – 1.03) times lower in vaccinated compared to unvaccinated individuals, with P=0.09. The overall vaccine efficacy (VE) was 15% (95% CI -3 – 30). Conclusion: There was no statistically significant decrease in the chances of SARS-CoV-2 infection in vaccinated versus unvaccinated individuals. However, the overall vaccine efficacy was 15%.

We determined the levels of neutralizing antibodies against the SARS-CoV-2 ancestral strain, Delta and Omicron variants of concern (VOCs) in 125 healthcare workers, who received Coro-naVac as their primary vaccination and later received either a single ChAdOx1 or a combination of two consecutive boosters using either two ChAdOx1 doses or a ChAdOx1 or BNT162b2 as the primary and second boosters, respectively, or 2 doses of BNT162b2. The titers 12 weeks after primary vaccination were inadequate to neutralize the all strains. After a single ChAdOx1 boost-er, the levels of neutralization at Day 30 varied significantly, only a small proportion of partici-pants developing neutralizing titers against Omicron at Day 7 and 30. The two doses of ChA-dOx1 as the booster induced lowest activity. A combination ChAdOx1 and BNT162b2 induced greater neutralization than by two doses of ChAdOx1. Two doses of BNT162b2 as the booster had the maximal activity against Omicron VOC.

The 10-valent pneumococcal vaccine was introduced in Pakistan’s Expanded Program on Immunization (EPI) in 2013 as a 3+0 schedule without catchup. We conducted three annual cross-sectional surveys from 2014-2016 to measure vaccine-type (VT) carriage in infants from a rural part of Pakistan. Nasopharyngeal specimens were collected by random sampling of infants from 2 union councils of Matiari. Samples were then transported to Infectious Disease Research Laboratory (IDRL) at the Aga Khan University within 6-8 hours of collection. Serotypes were established using sequential multiplex PCR. Of the 665 children enrolled across three surveys, 547 were culture positive for pneumococcus. VT carriage decreased from 21·8% in 2014 to 12·7% in 2016 (p-value for trend <0·001). Those who were not vaccinated or partially vaccinated were found to be at higher risk of carrying a VT serotype (aOR 2·53, 95% CI 1·39, 4·63 for non-vaccinated) and (aOR 3·35, 95% CI 1·82, 6·16 for partially vaccinated). On the other hand, being enrolled in the most recent survey was negatively associated with VT-carriage (aOR 0·51, 95% CI 0·28, 0·93). We found that PCV10 was effective in decreasing the carriage of vaccine-type serotypes in Pakistani infants.

The COVID-19 pandemic has highlighted the adverse consequences created by an infodemic specifically on compliance with public health guidance and vaccine uptake. COVID-19 vaccine hesitancy is a complex construct that is related to health beliefs, misinformation exposure, and perceptions of governmental institutions. This study draws on theoretical models and current data on the COVID-19 infodemic to explore the association between perceived risk of COVID-19, levels of misinformation endorsement, and opinions about the government response on vaccine uptake. We surveyed a sample of 2,697 respondents from the US, Canada, and Italy using a mobile platform between 21-28 May, 2021. Using multivariate regression, we found that country of residence, risk perception of contracting and spreading COVID-19, perception of government response and transparency, and misinformation endorsement was associated with the odds of vaccine hesitancy. Higher perceived risk was associated with lower odds of hesitancy, while lower perceptions of government response, and higher misinformation endorsement were associated with higher hesitancy.

The novel coronavirus disease (COVID-19) has created immense threats to public health on various levels around the globe. The unpredictable outbreak of this disease and the pandemic situation are causing severe depression, anxiety and other mental as physical health related problems among the human beings. To combat against this disease, vaccination is essential as it will boost the immune system of human beings while being in the contact with the infected people. The vaccination process is thus necessary to confront the outbreak of COVID-19. This deadly disease has put social, economic condition of the entire world into an enormous challenge. The worldwide vaccination progress should be tracked to identify how fast the entire economic as well as social life will be stabilized. The monitor ofthe vaccination progress, a machine learning based Regressor model is approached in this study. This tracking process has been applied on the data starting from 14^th December, 2020 to 24^th April, 2021. A couple of ensemble based machine learning Regressor models such as Random Forest, Extra Trees, Gradient Boosting, AdaBoost and Extreme Gradient Boosting are implemented and their predictive performance are compared. The comparative study reveals that the AdaBoostRegressor outperforms with minimized mean absolute error (MAE) of 9.968 and root mean squared error (RMSE) of 11.133.

Staphylococcus aureus mastitis remains a major challenge for dairy farming. Here, 24 mice were immunized and divided into four groups: G1: control; G2: Granulocyte Macrophage Colony-Stimulating Factor (GM-CSF) DNA vaccine; G3: F0F1 ATP synthase subunit α (SAS), succinyl-diaminopimelate (SDD), and cysteinyl-tRNA synthetase (CTS) recombinant proteins; and G4: SAS+SDD+CTS plus GM-CSF DNA vaccine. The lymphocyte subpopulations and the intracellular interleukin-17A (IL-17A) and interferon-γ production in the draining lymph node cells were immunophenotyped by flow cytometry. The immunophenotyping and lymphocyte proliferation was determined in spleen cells cultured with and without S. aureus stimulus. Immunization with S. aureus recombinant proteins generated memory cells in draining lymph nodes. Immunization with the three recombinant proteins plus GM-CSF DNA led to an increase in the percentage of IL-17A+ cells among overall CD44+ (memory), T CD4+, CD4+ T CD44+ CD27-, γδ TCR, γδ TCR+ CD44+ CD27+ and TCRVγ4+ cells. Vaccination with S. aureus recombinant proteins associated with GM-CSF DNA vaccine downregulates TH2 immunity. Immunization with the three recombinant proteins plus the GM-CSF DNA led to a proliferation of overall memory T, CD4+ and CD4+ TEM cells upon S. aureus stimulus. This approach fostered type 3 immunity, suggesting the development of a protective immune response against S. aureus.

Influenza B virus (IBV) is considered a major respiratory pathogen responsible for seasonal respiratory disease in humans, particularly severe in children and the elderly. Seasonal influenza vaccination is considered the most efficient strategy to prevent and control IBV infections. Live attenuated influenza virus vaccines (LAIVs) are thought to induce both humoral and cellular immune responses by mimicking a natural infection, but their effectiveness have recently come into question. Thus, the opportunity exists to find alternative approaches to improve overall influenza vaccine effectiveness. Two alternative IBV backbones were developed with re-arranged genomes, re-arranged M (FluB-RAM) and a re-arranged NS (FluB-RANS). Both re-arranged viruses showed temperature sensitivity in vitro compared to the WT type B/Bris strain, were genetically stable over multiple passages in embryonated chicken eggs and were attenuated in vivo in mice. In a prime-boost regime in naïve mice, both re-arranged viruses induced antibodies against HA with hemagglutination inhibition titers considered of protective value. In addition, antibodies against NA and NP were readily detected with potential protective value. Upon lethal IBV challenge, mice previously vaccinated with either FluB-RAM or FluB-RANS were completely protected against clinical disease and mortality. In conclusion, genome re-arrangement renders efficacious LAIV candidates to protect mice against IBV.

Middle East Respiratory Syndrome coronavirus (MERS-CoV) infects dromedary camels and zoonotically infects humans, causing a respiratory disease with severe pneumonia and death. With no approved antiviral or vaccine interventions for MERS, vaccines are being developed for camels to prevent virus transmission into humans. We have previously developed a chimpanzee adenoviral vector-based vaccine for MERS-CoV (ChAdOx1 MERS) and reported its strong humoral immunogenicity in dromedary camels. Here, we looked back at total RNA isolated from three immunised dromedaries pre and post-vaccination during the first day; and performed RNA sequencing and bioinformatic analysis in order to shed light on the molecular immune responses following a ChAdOx1 MERS vaccination. Our finding shows that a number of transcripts were differentially regulated as an effect of the vaccination, including genes that are involved in innate and adaptive immunity, such as type I and II interferon responses. The camel Bcl-3 and Bcl-6 transcripts were significantly upregulated, indicating a strong activation of Tfh cells, B cell, and NF-kB pathways. In conclusion, this study gives an overall view of the first changes in the immune transcriptome of dromedaries after vaccination; it supports the potency of ChAdOx1 MERS as a potential camel vaccine to block transmission and prevent new human cases and outbreaks.

Sexually transmitted infections (STIs) such as Gonorrhea is associated with serious morbidity and mortality rates in the world considering the multiple virulence factors possessed. The disease is manifested as salpingitis, pelvic inflammatory disease (PID), and bacteremia and is controlled by macrophages, dendritic cells, neutrophils, T cells, epithelial cells and cytokines. Dihydroliponamide acetyltransferase, a component of the mitochondrial pyruvate complex can be used as immunogenic target. Recent changes in the strain allowed the bacteria to acquire resistance against antibiotics.Vaccination remains an alternative to prevention against the disease. This study predicts an effective epitope-based vaccine against dihydrolipoamide acetyltransferase of Neisseria Gonorrhea using immunoinformatics approaches. Sequences retrieved from NCBI were passed on several prediction tests to analyze for possible B-cell, T-cell MHC class I epitopes and class II. Two epitopes showed high binding affinity for B-cells, while thirteen epitopes showed high binding affinity for MHCI and forty-five for MHCII. A population coverage of 100% for combined MHC I and II dictates the huge number of individuals who will benefit from formulating the vaccine. We recommend invivo and invitro studies to prove our prediction results.

This review will explore the four major pillars required for design and development of an saRNA vaccine: antigen design, vector design, non-viral delivery systems, and manufacturing (both saRNA and lipid nanoparticles (LNP)). In will report on the major innovations, preclinical and clinical data reported in the last five years and will discuss future prospects.

Bacillus Calmette-Guérin (BCG) vaccine is the only licensed vaccine against tuberculosis (TB) in humans and animals. It is most commonly administered parenterally but oral delivery is highly advantageous for immunisation of cattle and wildlife hosts of TB in particular. Since BCG is susceptible to inactivation in the gut, vaccine formulations were prepared from suspensions of Eudragit L100 copolymer powder and BCG in PBS, containing Tween 80, with and without the addition of mannitol or trehalose. Samples were frozen at -20oC, freeze-dried and the lyophilised powders were compressed to produce BCG-Eudragit matrices. Production of the dried powders resulted in a reduction in BCG viability. Substantial losses in viability occurred at the initial formulation stage and at the stage of powder compaction. Data indicated that the Eudragit matrix protected BCG against simulated gastric fluid (SGF). The matrices remained intact in SGF and dissolved completely in SIF within three hours. The inclusion of mannitol or trehalose in the matrix provided additional protection to BCG during freeze-drying. Control needs to be exercised over BCG aggregation, freeze-drying and powder compaction conditions to minimise physical damage of the bacterial cell wall and maximise the viability of oral BCG vaccines prepared by dry powder compaction.

Dengue virus (DENV), the causative agent of dengue fever (DF), is one of the most important mosquito-borne viruses that can infect humans. Although much effort has been made on prevention and control of dengue, there are currently no anti-viral drugs or worldwide approved vaccines yet. In this study, we immunized six-week-old Balb/c mice with DNA vaccine candidates E and NS1-2a of DENV serotype 2 or the combination of them (E+NS1-2a) via an electroporation (EP)-assisted intramuscular gene delivery system and evaluated the immune response and protection. The highest specific antibody titres and cytokine levels secreted by splenocytes as well as the highest survival rate were observed in the E+NS1-2a group, followed by E group and NS1-2a group. Our data suggested that the combination of E and NS1-2a delivered by EP may be a superior preventive strategy against DENV.

All vaccines exhibit specific and nonspecific effects. Specific effects are shown by the efficacy against the target pathogen, while nonspecific effects can be detected by the change in all-cause mortality. The real-world non-COVID-19 all-cause mortality (NCACM) data for the population of England between January 2021 and May 2023 was assessed. All vaccines administered were based on the original Wuhan antigen. Each gender and age group, along with COVID-19 variant shows its own unique NCACM vaccination benefit/disbenefit time profile. The efficacy of COVID-19 vaccination against COVID-19 disease/death per se is undisputed, however, the nonspecific outcomes of COVID–19 vaccination is far more nuanced than have been widely appreciated. This confirms an earlier study on the unanticipated nonspecific effects of influenza vaccination against all-cause winter mortality. Interestingly, a high proportion of NCACM beneficial effects occurred during the first 21 days following COVID-19 vaccination, while the worst example of increased NCACM occurred during the fourth dose of COVID-19 vaccination in 19–40-year-olds for the interval &gt;21 days post vaccination which led to NCACM 3- to 10-times higher than in the unvaccinated. By the time of the Omicron variant, NCACM outcomes in those aged 90+ are mostly adverse. The beneficial nonspecific effects of COVID-19 vaccination increase with age and reach their maximum effect during the second week post vaccination for age groups below 50 years, rising to during the third week for those aged 70+. Finally, we discuss the mechanisms by which COVID-19 vaccination could induce wider nonspecific effects. Most of these mechanisms seem to depend on gene regulation by noncoding RNAs which also interact with mRNAs. We suggest that further international studies are required to discern the nonspecific NCACM effects of the different COVID-19 variants other than the three variants prevalent in the UK, and different types/manufacturer of COVID-19 vaccines which have been employed around the world. We can only speculate regarding the nonspecific effects of the COVID-19 vaccines administered to persons with an asymptomatic infection, and during vaccine waning. Vaccines not only need to be effective against the target pathogen, as primarily determined by antibody production, but need to minimize any unanticipated adverse nonspecific effects against all-cause mortality.

To develop a modern plague vaccine, we used hypo-endotoxic Yersinia pestis bacterial ghosts (BGs) with combinations of genes encoding the bacteriophage ɸX174 lysis-mediating protein E and/or holin-endolysin systems from λ or L-413C phages. Expression of the protein E gene resulted in the BGs that retained the shape of the original bacterium. Co-expression of this gene with genes coding for holin-endolysin system of the phage L-413C caused formation of structures resembling collapsed sacs. Such structures, which have lost their rigidity, were also formed as a result of the expression of only the L-413C holin-endolysin genes. Similar holin-endolysin system from phage λ containing mutated holin gene S and intact genes R-Rz coding for the endolysins caused generation of mixtures of BGs that had (i) practically preserved and (ii) completely lost their original rigidity. The addition of protein E to the work of this system shifted the equilibrium in the mixture towards the collapsed sacs. The collapse of the structure of BGs can be explained by endolysis of peptidoglycan sacculi. Immunizations of laboratory animals with the variants of BGs followed by infection with a wild-type Y. pestis strain showed that bacterial envelopes protected only cavies. BGs with peptidoglycan maximally hydrolyzed had a greater protectivity compared to BGs with preserved peptidoglycan skeleton.

Background: Having a laboratory renal profile for medical imaging examinations requiring contrast media (CM) administration is strongly advised. Creatinine helps identify patients at risk of contrast-induced nephropathy (CIN). GEM® Premier™ ChemSTAT (Werfen) is a point-of-care (POC) analyzer with 12 emergency parameters including creatinine assay. The aim of this study consists to compare ChemSTAT with the central analytical solution of the University Hospital of Clermont-Ferrand and to evaluate the interest of the POC creatinine in the emergency department (ED) in optimizing the flow of patients, especially if CM used. Methods: More than 200 whole blood (WB) samples from the ED were evaluated on the ChemSTAT analyzer. As comparative methods, the plasma aliquots from the same samples were assayed on an Atellica® CH (Siemens Healthineers). The clinical concordance was assessed ac-cording the decision cut-offs of the French Society of Radiology for the risk of CIN. The availability times of biological results between ChemSTAT and the central laboratory were studied. Results: WB results from ChemSTAT correlated well with those from Atellica® CH, except for tCO2 (known bias between Siemens and Cobas Roche methods predicting ChemSTAT values). The results of creatinine assay allow to have identical medical decisions compared to the renal risk cut-offs. The availability of biological results is reduced by 50 min on average with ChemSTAT vs the central laboratory. Computed tomography was performed for 44.7% of patients including the injection of the CM in 68% of cases. For these patients, the availability of creatinine results relative to imaging time is faster with the ChemSTAT on average of 45.2 min. Conclusions: Great analytical and clinical correlations for creatinine assay allow safe iden-tification of patients at risk of CIN and improve patient flow in ED especially for those requiring computed tomography with use of CM.

The present study analyses the influence of scratches and fatigue on the mechanical characteristics of aluminium alloys commonly used in the aviation industry: 2024-T4, 6061-T4, 6061-T4 uncoated, 6061-T6 uncoated, 7075-T0, and 7076-T6. 120 specimens were used for the study. Out of these, 60 samples were scratched, and the other 60 samples were also scratched under the same circumstances and then subjected to low-cycle fatigue (LCF) before undergoing the tensile test. Based on the statistical examination of the measured data, mathematical prediction models have been established. Compared to their unscratched counterparts, the results indicate a significant decrease in the mechanical properties of both scratched and scratched-fatigued sample sets. The LCF pre-treatment contributes to the negative impacts of scratches, resulting in a reduced value for the ultimate tensile strength and elongation at break. The results conclude that surface integrity plays an essential role in preserving aircraft components' structural strength.

Treatment of osteochondritis dissecans of the knee, has always been a challenge for orthopedic surgeons. We present a case report of a 38-year-old male with severe right knee pain after suffering from an indirect trauma and axial rotation of the knee, limiting knee functionality and impeding ability to walk, with diagnosis of osteochondritis dissecans in the trochlea of the knee, who underwent arthroscopic treatment with matrix induced autologous chondrocyte implantation (MACI). After the surgery, physical therapy protocol for MACI was implemented, magnetic imagen resonance images with cartilage mapping were used to evaluate recovery of the lesion. A total recovery was observed evaluated with the modified Cincinnati knee rating system (mCKRS). A discussion is provided with evidence and general recommendations for the use of MACI in the treatment of adult OCD of the knee.

Crystallization of glass through conventional thermal annealing in a furnace is a well-understood process. However, crystallization by femtosecond (fs) laser brings another dimension to this process. The pulsed nature of the irradiation necessitates a reevaluation of parameters for optimal crystallization and to understand the particularities in the case of using fs laser. This includes adjusting the laser pulse energy, the repetition rate, and the writing speed to either initiate nucleation or achieve substantial crystal growth. Therefore, a key challenge to this work is to establish reliable calculations for understanding the relation of the size of the crystallized region with respect to an ongoing transition (e.g., solid-to-solid, liquid-to-solid), and accounting for the aforementioned laser parameters. In this context and based on previous work, we simulate a temperature distribution (in space and time) to model the thermal treatment at any point in the glass. By setting the condition that the temperatures are between the glass transition and melting temperature, we can deduce the crystallized region size to be compared with experimental observations. For that purpose, the knowledge of the beam width at the focal point and of the absorbed beam energy fraction are critical inputs that were extracted from experiments found in the literature. After that, management of the crystallization process and the width of the crystallization line can be achieved according to pulse energy e.g. crystallite size, and also the effect of the scanning speed can be understood. Among the main conclusions to highlight, we disclose the laser conditions that determine the extent of the crystallized area and deduce that it is never interesting to increase the pulse energy too much but rather the repetition rate for uniform crystallized line.

Mechanical ventilation (MV), used in patients with acute lung injury (ALI), induces diaphragmatic myofiber atrophy and contractile inactivity, termed ventilator-induced diaphragm dysfunction. Phosphoinositide 3-kinase- (PI3K-) is crucial in modulating fibrogenesis during the reparative phase of ALI; however, the mechanisms regulating the interactions among MV, myofiber fibrosis, and PI3K- remain unclear. We hypothesized MV with or without bleomycin treatment would increase diaphragm muscle fibrosis through the PI3K- pathway. Five days after receiving a single bolus of 0.075 units bleomycin intratracheally, C57BL/6 mice were exposed to 6 or 10 mL/kg MV for 8 h after receiving 5 mg/kg of AS605240 intraperitoneally. In wild-type mice, bleomycin exposure followed by MV 10 mL/kg prompted significant increases in disruptions of diaphragmatic myofibrillar organization, transforming growth factor-1, oxidative loads, Masson’s trichrome staining, extracellular collagen levels, positive staining of -smooth muscle actin, PI3K- expression, and myonuclear apoptosis (P &lt; 0.05). Decreased diaphragm contractility and peroxisome proliferator activated receptor- coactivator-1 levels were also observed (P &lt; 0.05). MV-augmented bleomycin-induced diaphragm fibrosis and myonuclear apoptosis were attenuated in PI3K-γ-deficient mice and through AS605240-induced inhibition of PI3K- activity (P &lt; 0.05). MV-augmented diaphragm fibrosis after bleomycin-induced ALI is partially mediated through PI3K-γ. Therapy targeting PI3K-γ may ameliorate MV-associated diaphragm fibrosis.

Luminescent carbon dots (CDs) were locally synthesized in the core of CYTOP fibers using IR femtosecond laser direct writing (FLDW), a one-step simple method serving as a post-treatment of the genuine fiber. This approach enables the creation of several types of modifications such as ellipsoid voids. The CDs and photoluminescence (PL) distribute at the periphery of the voids. The PL spectral properties were studied through Excitation Emission Matrix in the visible range and excitation/emission spectrum in UV/visible range. Our finding reveals the presence of at least 3 distinct luminescent species, facilitating a broad excitation range extending from UV to green, and light emission spanning from blue to red. The average laser power and dose influence the quantity and ratio of these luminescent CD species. Additionally, we measured the spatially resolved lifetime of the luminescence during and after the irradiation. We found longer lifetimes at the periphery of the laser-induced modified regions and shorter ones closer to the center, with a dominant lifetime ~ 2ns. Notably, unlike many other luminophores, these laser-induced CDs are insensitive to oxygen, enhancing their potential for display or data storage applications.

In this study, we define screening maps for Italy that classify sites based on their potential for triggering landslides. To this end, we analyze seismic hazard maps and hazard disaggregation results on a national scale considering four spectral periods (0.01s, 0.2s, 0.5s, and 1.0s) and three return periods (475, 975, and 2475 years). First, joint distributions of magnitude (M) and distance (R) from hazard disaggregation are analyzed by means of an innovative approach based on image processing techniques to find all modal scenarios contributing to the hazard. In order to obtain the M-R scenarios controlling the triggering of earthquake-induced landslides at any computation node, mean and modal M-R pairs are compared to empirical curves defining the M-R bounds associated with landslide triggering. Three types of landslides are considered (i.e., disrupted slides and falls, coherent slides, and lateral spreads and flows). As a result, screening maps for all of Italy showing the potential for triggering landslides based on the level of seismic hazard are obtained. The maps and the related data are freely accessible at the following web address: https://distav.unige.it/rsni/slideq.php.

Introduction: Substance-induced psychotic disorder (SIPD) is a mental health condition linked to the use of a psychotropic substance whose pathogenesis has not been totally clarified. The present retrospective observational study has the objective to identify differences in clinical features and peripheral biomarkers in SIPD patients according to the main substance of abuse.Methods: A total sample of 218 patients was divided in 3 groups according to the type of consumed substance: alcohol, cannabis and psychostimulants. The 3 groups were compared for continuous variables by one-way analyses of variance (ANOVAs) and for qualitative variables by χ² tests. After removing alcohol-induced psychotic disorder group, the same analyses were repeated. Statistically significant variables from these latter analyses were included in a binary logistic regression model to confirm their reliability as predictors for cannabis- or psychostimulants-induced psychotic disorders. Results: Psychotic cannabis abusers were younger (p<0.01) and had an earlier age at onset (p<0.01). On the contrary, alcohol consumers resulted to have a longer duration of illness (p<0.01), more previous hospitalizations (p=0.04), more frequent medical comorbidity (p<0.01), higher mean Modified Sad Person Scale scores (p<0.01). Finally, psychostimulant abusers had more frequently a lifetime history of poly-substance use disorders (p<0.01). Binary logistic regression revealed that higher mean Brief Psychiatric Rating Scale scores (p<0.01) higher sodium (p=0.012) and haemoglobin(p=0.040) plasma levels were predictors of cannabis misuse in SIPD patients.Conclusions: Different clinical factors and biochemical parameters con be associated to SIPD according to the main substance of abuse, thus requiring a specific management by clinicians.

Modern engineering faces challenges in ensuring technical standards for service, durability, and sustainability. Political, administrative, and budgetary factors, coupled with climate change, pose tasks to structural integrity, affecting industries and economies. Marine infrastructures represent a strategic asset of the country as it handles a large part of the economic exchanges. This article analyzes five essential factors that play a fundamental role in the performance analysis of coastal structures: Chloride-induced corrosion, degradation models, maintenance strategies, monitoring, and climate change. Starting with reinforcement corrosion, considered as the main cause of distress, particularly in coastal zones for the long-term behavior of structures. Additional pressure from the influences of climate change is becoming evident and extreme, leading to reduction in capacity. To guarantee the lifespan, degradation models contribute by estimating the long-term performance of the asset as a strategic piece to the development of effective maintenance solutions. Additionally, quantifying the condition of the structure from monitoring data, plays a crucial part that provides information on the current situation of the structure. Finally, this review summarizes the challenges associated with the maintenance of aging marine structures considering aspects such as corrosion, monitoring, and the future challenges this area will face due to climate change.

2,4-dichlorophenoxyacetic acid (2,4-D) is a globally used herbicide and is frequently found in water samples. This fact has prompted studies on its effects in non-target organisms, revealing significant alterations on liver structure and function. In this review, we evaluated the literature on the hepatotoxicity of 2,4-D, focusing on morphological damages, biomarkers of toxicity and affected liver functions. Searches were conducted on PubMed, Web of Science and Scopus and 83 articles were selected after curation. Among the studies, 72% used in vivo models and 30% used in vitro models. Additionally, 48% used the active ingredient, and 35% used commercial formu-lations in exposure experiments. The most affected biomarkers were related to a decrease in an-tioxidant capacity, including alterations in the activities of catalase and superoxide dismutase, and in the levels of malondialdehyde. Changes in energy metabolism, lipids, liver function, and xenobiotic metabolism were also identified. Furthermore, we found studies about the effects of 2,4-D in mixtures with other pesticides, as well as hepatoprotection trials. The reviewed data in-dicate that the reduction in antioxidant capacity and oxidative stress play an important role in 2,4-D-induced hepatotoxicity. However, the mechanism of action of the herbicide is still not ful-ly understood and further research in this area is needed.

Photodynamic therapy (PDT) has garnered significant attention in the fields of cancer treatment and drug-resistant bacteria eradication due to its non-invasive nature and spatiotemporal controllability. Iridium complexes have captivated researchers owing to their tunable structure, exceptional optical properties, and substantial Stokes displacement. However, most of these complexes suffer from aggregation-induced quenching, leading to diminished luminous efficiency. In contrast to conventional photosensitizers, photosensitizers exhibiting aggregation-induced luminescence (AIE) properties retain the ability to generate a large number of reactive oxygen species when aggregated. To overcome these limitations, we designed and synthesized a novel iridium complex named Ir-TPA in this study. It incorporates quinoline triphenylamine cyclomethylated ligands that confer AIE characteristics for Ir-TPA. We systematically investigated the photophysical properties, AIE behavior, spectral features, and reactive oxygen generation capacity of Ir-TPA. The results demonstrate that Ir-TPA exhibits excellent optical properties with pronounced AIE phenomenon and robust capability for producing singlet oxygen species. This work not only introduces a new class of metal iridium complex photosensitizer with AIE attributes but also holds promise for achieving remarkable photodynamic therapeutic effects in future cellular experiments and biological studies.

Transit-oriented development (TOD), such as metro depot and over-track building complexes, has expanded rapidly in China. Over-track building construction has the advantage of comprehensive utilization of land resources, ease of commuting to work, and provide funds for subway construction. However, there still has a pending problem, disturbance of railway vibration, for TOD. Excessive noise and vibration seriously affect people’s life. To address this challenge, field measurements are used to obtain the vibration source characteristics and vibration propagation of the ground and the superstructure in this study. And the typical metro depot with over-track building in Wuhan was selected. The effects of vibration on the surrounding ground and adjacent buildings caused by the operation of trains have been measured, and the propagation law of train-induced ground vibration acceleration in the time and frequency domains has been analyzed. The distribution and propagation laws of vibration noise, structural noise and secondary structure noise in sensitive areas such as the throat area, depot area, test section and access section of the over-track buildings and their impact laws on the over-track buildings are obtained. And the effectiveness of the vibration and noise reduction methods used were evaluated. Results show that within 43 m from the train running track, the train running induced vertical vibration acceleration level in the high-rise building peak size of 58.8 dB, the average value of 55.62 dB; vibration frequency components are mainly 40-60 Hz. The findings might provide useful insight for designing vibration mitigation systems in new metro depots with over-track buildings.

Target pests of genetically engineered crops producing both defensive allelochemicals and Bacillus thuringiensis (Bt) toxins often sequentially or simultaneously uptake allelochemicals, Bt toxins, and/or insecticides. How the three types of toxins interact to kill pests remains underexplored. Here we investigated the interactions of Bt toxin Vip3A, plant allelochemical flavone, and insecticide emamectin benzoate in Spodoptera frugiperda. Simultaneous administration of flavone LC25 + Vip3A LC25, emamectin benzoate LC25 + Vip3A LC25, and flavone LC15 + emamectin benzoate LC15 + Vip3A LC15 but not flavone LC25 + emamectin LC25 yielded a mortality significantly higher than their expected additive mortality (EAM). One-day preexposure to one toxin at LC5 followed by 6-day exposure to the same toxin at LC5 plus another toxin at LC50 showed that the mortality of flavone LC5 + Vip3A LC50, emamectin benzoate LC5 + Vip3A LC50, and Vip3A LC5 + emamectin benzoate LC50, were significantly higher than their EAM, while that of flavone LC5 + emamectin benzoate LC50 was significantly lower than their EAM. No significant difference existed among the mortalities of Vip3A LC5 + flavone LC50, emamectin benzoate LC5 + flavone LC50, and their EAMs. The results suggest that the interactions of the three toxins are largely synergistic (inductive) or additive, depending on their combinations and doses.

This paper deals with the quantitative analysis of measured fracture-induced electromagnetic radiation (FEMR) in the vicinity of the Dead Sea Transform using the Angel-M1 instrument, which enables the recording of FEMR signals in a 3D manner. Results show both the possibility of estimating the sizes of micro-fractures that are the sources of the radiation, and of assessing the direction of their location to the measuring device and the range of magnitude Mw of the impending "events" (EQ's) associated with the present FEMR measurements. Moreover, the relation between the measured FEMR activity (the number of FEMR hits per unit time) and the FEMR event magnitudes shows consistency with the Gutenberg-Richter relationship for the region. Such measurements could therefore constitute a preliminary 'field reinforcement' towards an EMR valid method for a real earthquake forecast, which would provide much earlier warnings than the seismic ones. Obviously, the present observed FEMR measurements can only be used as an assessment of the stress concentration and micro-fracturing in the region since they relate to the very initial nucleation phase of a "virtual" (extremely low Richter scale value) earthquake, but they do provide the necessary feasibility test for a prediction method since all lab-measured FEMR features were confirmed also in the field.

Cotton (Gossypium spp.) is a major source of natural fiber and an important cash crop. The cotton growth habit and architecture determine its productivity and influence management strategies for commercial production. The GATA transcription factors (TFs) control various developmental processes in plants, such as flower, bract and embryo development, and petal differentiation. As stable transformation is still a bottleneck in many plant species, TRV-VIGS was used to manipulate gene expression in different plants, including Gossypium hirsutum L. In this study, we undertook the TRV-based VIGS to functionally characterize two candidate genes, Gohir.D05G103700 and Gohir.D12G153600, identified through the expression QTL analysis for five floral induction and meristem identity genes using the upland cotton mini-core collection. Virus-induced silencing of the Gohir.D05G103700 gene resulted in up to a 1.4-fold reduction in the transcript level in two inoculated plants, G3 and G4, and Gohir.D12G153600 gene resulted in up to a 2.3-fold reduction in transcript level in a single inoculated plant P05 relative to the mock-treated plant. The TRV2-Gohir.D05G103700 inoculated plants precisely G3 and G4 also exhibited loss of the supernumerary (fourth) floral bract in the squares, whereas the TRV2-Gohir.D12G153600 inoculated plants did not show any observable phenotypic change relative to the mock-treated plants.  Altogether, this study suggested that TRV-VIGS can be used to characterize genes in cotton relatively rapidly and the cotton Gohir.D05G103700 gene is a positive regulator of the indeterminate growth habit in cotton, which could be manipulated to obtain a cotton plant with architecture best suited for the cultivation area.

Heavy metal contamination is listed among the most alarming threats to the environment and human health. The detrimental effects of heavy metals in the natural environment span from a reduction of biodiversity to toxic effects on marine life - through microplastic born heavy metals -, to impairment of microbial activity in the soil, and to detrimental effects on animal reproduction. A host of different chemical and biological technologies have been proposed to alleviate environmental contamination by heavy metals. Relatively less attention has been paid to the microbial precipitation of heavy metals, as a side mechanism of the most general process of microbially induced calcite precipitation (MICP). This process is currently receiving a great deal of interest from both a theoretical and practical standpoint, because of its possible practical applications in concrete healing and soil consolidation, and its importance in the more general framework of microbial induced mineral precipitation. In this study, we analyse the ability of the marine bacteria Vibrio harveyi in co-precipitating CaCO3 minerals, together with Cd, Cr, Pb, and Zn added in form of nitrates, from solutions containing CaCl2. The precipitated carbonatic minerals were a function of the different heavy metals present in the solution. The process of co-precipitation appears to be rather effective and fast, as the concentrations of the 4 heavy metals were reduced in 2 days by 97.2%, on average, in the solutions.

A single paragraph of about 200 words maximum. For research articles, abstracts should give a pertinent overview of the work. We strongly encourage authors to use the following style of structured abstracts, but without headings: (1) Background: Place the question addressed in a broad context and highlight the purpose of the study; (2) Methods: briefly describe the main methods or treatments applied; (3) Results: summarize the article's main findings; (4) Conclusions: indicate the main conclusions or interpretations. The abstract should be an objective representation of the article and it must not contain results that are not presented and substantiated in the main text and should not exaggerate the main conclusions.

Direct cardiac reprogramming of fibroblasts into induced cardiomyocytes (iCMs) is a promising approach but remains a challenging technology of regenerative medicine for damaged myocardium. Efforts have been focused on improving the efficiency by understanding fundamental mechanisms. One of the major challenges is that the plasticity of cultured fibroblast varies batch to batch with unknown mechanisms. Here, we noticed that a portion of in vitro cultured fibroblasts have been activated to differentiate into myofibroblasts, marked by the expression of αSMA, even in the primary cell culture of tissues. Both forskolin, which activates adenylyl cyclase and increases cAMP concentration, and TGFbeta inhibitor SB431542 can efficiently suppress myofibroblast differentiation of cultured fibroblasts. However, SB431542 improved but forskolin blocked iCM reprogramming of fibroblasts that were infected with retroviruses of Gata4, Mef2c and Tbx5 (GMT). Moreover, inhibitors of cAMP downstream signaling pathways, PKA or CREB-CBP, significantly improved the efficiency of iCM reprogramming. Consistently, inhibition of p38/MAPK, another upstream regulator of CREB-CBP, also improved reprogramming efficiency. We then investigated if inhibition of these signaling pathways in primary cultured fibroblast could improve their plasticity for reprogramming, and found that preconditioning of cultured fibroblasts with CREB-CBP inhibitor significantly improved the cellular plasticity of fibroblasts to be reprogrammed, yielding ~2-fold amount of reprogrammed iCMs compared to that of untreated control cells. In conclusion, suppression of cAMP/PKA/CREB signaling axis improves fibroblast plasticity for direct cardiac reprogramming.

Regenerative medicine aims to repair damaged or missing cells, tissues or organs for the treatment of various diseases, poorly managed with conventional drugs and medical procedures. To date there are different approaches to obtain these results. Multimodal regenerative methods include transplant of healthy organs, tissues, or cells, body stimulation to activate a self healing response in damaged tissues, as well as the combined use of cells and bio-degradable scaffold to obtain functional tissues. Certainly, stem cells and derived products are promising tools in regenerative medicine due to their ability to induce de novo tissue formation and/or promote tissue and organ repair and regeneration. Currently, several studies have shown that the beneficial stem cell effects in damaged tissue restore are not depending on their engraftment and differentiation on the injury site, but rather to their paracrine activity. It is now well known that paracrine action of stem cells is due to their ability to release Extracellular Vesicles (EVs). EVs play a fundamental role in cell-to cell communication and are directly involved in tissue regeneration. In the present review, we tried to summarize the molecular mechanisms trough which EVs carry out their therapeutic action and their possible application for the treatment of several diseases.

In this paper, we consider the temporal development of the optical density of the H$_\alpha$ spectral line in a hydrogen laser induced plasma. This is achieved by using the so-called duplication method in which the spectral line is re-imaged onto itself and the ratio of the spectral line with it duplication is taken to its measurement without the duplication. We asses the temporal development of the self-absorption of the H$_\alpha$ line by tracking the decay of duplication ratio from its ideal value of 2. We show that when 20% loss is considered along the duplication optical path length, the ratio is 1.8 and decays to a value of 1.25 indicating an optically thin plasma grows in optical density to an optical depth of 1.16 by 400 ns in the plasma decay for plasma initiation conditions using Nd:YAG laser radiation at 120 mJ per pulse in a 1.11$\times10^{5}$ Pa hydrogen/nitrogen gas mixture environment. We also go on to correct the H$_\alpha$ line profiles for the self-absorption impact using two methods. We show that a method in which the optical depth is directly calculated from the duplication ratio is equivalent to standard methods of self-absorption correction when only relative corrections to spectral emissions are needed.

Pomegranate peel is a natural source of phenolics, claimed to possess healing properties, among which antioxidant and antidiabetic. In line with this evidence, the ethyl acetate PGE extract, obtained by Soxhlet from the peel of Dente di cavallo DC2 variety and characterized by a 4% amount of ellagic acid, has been studied for its hypoglycemic, antiglycation and antioxidative cytoprotective properties, in order to support a possible further nutraceutical interest. The α-amylase and α-glucosidase enzyme inhibition, interference with advanced glycation end-products (AGE) formation and metal chelating abilities were evaluated as hypoglycemic mechanisms. Also, considering that oxidative stress is associated with hyperglycemia complications, PGE antioxidant cytoprotective properties under hyperglycemic conditions were assayed. Phenolic profile was characterized by integrated chromatographic and spectrophotometric methods. Under our experimental conditions, PGE strongly inhibited the tested enzymes, especially α-glucosidase, and exerted chelating and antiglycation properties. Also, it reduced both ROS and GSH levels under hyperglycemic conditions, thus suggesting its ability to support cell functions by counteracting intracellular oxidative stress. Along with ellagic acid, rutin was the major identified flavonoid (about 4 %) of PGE. Present results suggest PGE to be a possible remedy for hyperglycemia management and encourage further studies to exploit its promising properties.

In intermediary metabolism, enzymes are mainly for the specific provision of one small molecule from another, B from A, for its further use. But there are also decades of work relating to another evolved purpose, which is to prevent untoward effects of odd compounds of various origins, and of ordinary intermediates, whose improper concentrations may be avoided by hydrolases and other activities of metabolic correction.

Background: In hepatocytes and alcohol-metabolizing cultured cells, Golgi undergoes ethanol (EtOH)-induced disorganization. Periniclear and organized Golgi is important in liver homeostasis, but how the Golgi remains intact is unknown. Work from our laboratories showed that EtOH-altered cellular function could be reversed after alcohol removal; we wanted to determine whether this recovery would apply to Golgi. Methods: We used alcohol-metabolizing HepG2 (VA-13) cells (cultured with or without EtOH for 72 h) and rat hepatocytes (control and EtOH-fed (Lieber-DeCarli diet). For recovery, EtOH was removed and replenished with control medium (48 hours for VA-13 cells) or control diet (10 days for rats). Results: EtOH-induced Golgi disassembly was associated with de-dimerization of the largest Golgi matrix protein giantin, along with impaired transport of selected hepatic proteins. After recovery from EtOH, Golgi regained their compact structure, and alterations in giantin and protein transport were restored. In VA-13 cells, when we knocked down giantin, Rab6a GTPase or non-muscle Myosin IIB, minimal changes were observed in control conditions, but post-EtOH recovery was impaired. Conclusions: These data provide a link between Golgi organization and plasma membrane protein expression and identify several proteins whose expression is important to maintain Golgi structure during the recovery phase after EtOH administration.

This work examines atomic and molecular signatures in laser-induced plasma in standard ambient temperature and pressure environments, including background contributions to the spectra that depend on the laser pulse-width. Investigations include solids, gases, and nano-particles. Abel inversions of measured line-of-sight data reveal insight into the radial plasma distribution. For nominal 6 nanosecond laser pulses and for pulse-energies in the range of 100 to 800 milli-Joules, expansion dynamics and turbulence due to shock phenomena are elucidated to address local equilibrium details that are frequently assumed in spatially averaged emission spectroscopy. Chemical equilibrium computations reveal temperature dependence of selected plasma species. Specific interests include atomic hydrogen (H) and cyanide (CN). The atomic H spectra, collected following optical breakdown in ultra-high-pure hydrogen and 9:1 mixtures of ultra-pure hydrogen and nitrogen gases, indicate spherical shell structures and isentropic expansion of the plasma kernel over and above the usual shockwave. The recombination radiation of CN emanates within the first 100 nanoseconds for laser-induced breakdown in a 1:1 CO₂:N₂ gas mixture when using nanosecond laser pulses to create the micro-plasma. The micro-plasma is generated using 1064 nm, 150 mJ, 6 ns Q-switched Nd:YAG laser radiation. Measurements of the optical emission spectra utilize a 0.64 m Czerny-Turner type spectrometer and an intensified charge-coupled device.

Background and objectives: Contrast-induced nephropathy (CIN), is an acute renal damage due to contrast agents. This study is conducted to determine the potential diagnostic value of hypoxia-inducible factor 2-alpha (HIF2-α) and to evaluate the renal protective effects of N-acetyl cysteine (NAC) and sildenafil in a rat CIN model. Material/Methods: This randomized, controlled, interventional animal study was conducted on Wistar rats. Totally, rats (n = 36) were randomly assigned to four groups: control (n = 9), CIN group (n = 9), CIN+NAC group (n = 9), and sildenafil (n = 9). The rat model was used to form iohexol-originated CIN. During the modelling, prophylactic treatment was performed at 24th and 48th hours. After 48 hours of the modelling; blood, urine, tissue samples were obtained for biochemical analyses. HIF-2-α levels were measured in renal tissue, serum and urine samples. Renal sections were performed in order for histopathologic and immunohistochemical evaluations. Results: In the CIN model, HIF-2α levels and other biochemical parameters were significantly increased (p < 0.01). Both sildenafil and NAC, efficiently decreased the renal damage due to contrast agents (p < 0.05). Similarly, after treatment with sildenafil and NAC, HIF-2α levels were significantly decreased (p < 0.05). Conclusions: The current study constructs an experimental base for the use of HIF-2α for clinical prevention and treatment of CIN. Several mechanisms may be postulated for the changes in HIF-2α levels. Besides, the increased HIF-2α levels with CIN and decreased HIF-2α levels after treatment may be used for the treatment and follow-up of patients with CIN.

Vaccines decrease morbidity and mortality. Nevertheless, their benefits depend on public response. During COVID-19, vaccine hesitancy and refusal were rampant, threatening public health. A thorough understand-ing of opponents' arguments is required to address the diffusion of unreliable information on social media and prevent vaccine hesitancy from developing into vaccine refusal. Accordingly, the article examines vac-cine opponents' justifications on social media. Textual content analysis of reader comments on three health-related Israeli Facebook pages was conducted. Data collection encompassed the Israeli COVID-19 vaccination period from October 2020 to May 2022. The comments were analyzed according to the health beliefs model (HBM). We found that vaccine opponents were characterized by low perceptions of the severity of the disease combined with high perceptions of the damages of the vaccine; low perceived benefits of vac-cine compliance; vaccine hesitancy and fear along with public distrust as barriers to change; and call for ac-tion to resist the vaccine and spread related anti-establishment views on the web. As vaccination hesitancy was found to develop into public distrust in the state systems and escalate into conspiracy beliefs and an-ti-vaccination activism, its early detection may prevent future vaccine resistance.

Background: we aim to investigate attitudes toward vaccination, by analyzing empirical factors associated with vaccine acceptance in the Lazio region mpox vaccination (MpoxVax) campaign in Italy. Methods: all subjects who accessed to MpoxVax and signed the informed consent were prospectively enrolled in the MPOX-VAC Study and were asked to fill out an anonymous survey. Two endpoints were selected: ‘delayed acceptance’ and ‘early acceptance’, defined as access for vaccination &gt;60 and ≤30 days from the vaccination campaign starting (VCS), respectively. Results: over the study period 1717 individuals underwent vaccination: 129 (7%) &gt;60 [1588 (92.5%) ≤60] and 676 (60%) ≤30 days from VCS. A bisexual orientation, a lower education level and a worse perceived physical and mental health were associated with delayed access to vaccination. Being Pre-Exposure Prophylaxis (PrEP) users and, marginally, HIV positive, having a high perceived risk for mpox infection and reporting high-risk behaviors like the use of recreational drugs/chems, sex under the influence of drugs and/or alcohol and higher number of principal sexual partners, were associated with early access to vaccination. Conclusions: according to our data, risk awareness was a major determinant of early mpox vaccination acceptance. Conversely, worse perceived health status and a low educational level were critical factors associated with delayed vaccination.

Qatar experienced five SARS-CoV-2 waves dominated sequentially by the original virus, Alpha, Beta, Omicron BA.1 and BA.2, and Omicron BA.4 and BA.5, in addition to a prolonged low-incidence phase dominated by the Delta variant. The two-dose primary series of BNT162b2 (Pfizer-BioNTech) COVID-19 vaccine against SARS-CoV-2 infection has been approved for use in 10µg formulations among children and adolescents aged 12-17 years as of May 16, 2021. This study aimed at estimating the effectiveness of the 30µg BNT162b2 Pfizer-BioNTech mRNA COVID-19 vaccine against the pre-Omicron variants of SARS-CoV-2 infection in children and adolescents aged 12-17 years residing in Qatar. A test-negative matched case-control study was conducted where any child or adolescent aged 12-17 years who had been tested for SARS-CoV-2, RT-PCR tests performed on nasopharyngeal or oropharyngeal swabs, as part of contact tracing, between June and November 2021 and eligible to receive the BNT162b2 vaccine as per the national guidelines. Data regarding 14,161 children/adolescents meeting inclusion-exclusion criteria were retrieved from the national Surveillance and Vaccine Electronic System (SAVES). Of the total, 3.1% (444) were positive for SARSCoV-2. More than half (55.96%) were vaccinated with two doses of Pfizer-BioNTech-mRNA COVID-19 vaccine. Amongst those immunized with two doses, 1.2% tested positive for SARS CoV2, while 5.6% amongst the unvaccinated tested positive. The vaccine effectiveness was calculated to be 79%. Pfizer-BioNTech mRNA COVID-19 vaccine provides protection from COVID-19 infection for children/adolescents, hence it is crucial to ensure they receive the recommended vaccines.

Generating long-lived mucosal and systemic antibodies through respiratory immunization with protective antigens encapsulated in nanoscale biodegradable particles could potentially decrease or eliminate the incidence of many infectious diseases but requires incorporation of a suitable mucosal immunostimulant. We previously found that respiratory immunization with a model protein antigen (LPS-free OVA) encapsulated in PLGA 50:50 nanoparticles (~380 nm diameter) surface modified with complement peptide-derived immunostimulant 02 (CPDI-02; formerly EP67) through 2kDa PEG linkers increases mucosal and systemic OVA-specific memory T-cells with long-lived surface phenotypes in young, naïve female C57BL/6 mice. Here, we determined if respiratory immunization with LPS-free OVA encapsulated in similar PLGA 50:50 microparticles (~1 μm diameter) surface modified with CPDI-02 (CPDI-02-MP) increases long-term OVA-specific mucosal and systemic antibodies. We found that, compared to MP surface modified with inactive, scrambled scCPDI-02 (scCPDI-02-MP), intranasal administration of CPDI-02-MP in 50 μL sterile PBS greatly increased titers of short-term (14 days post-immunization) and long-term (90 days post-immunization) antibodies against encapsulated LPS-free OVA in nasal lavage fluids, bronchoalveolar lavage fluids, and sera of young, naïve female C57BL/6 mice. Thus, surface modification of biodegradable microparticles with CPDI-02 is likely to increase long-term mucosal and systemic antibodies against encapsulated protein antigen after respiratory and possibly other routes of mucosal immunization.

In Morocco, cervical cancer is the second most frequent cancer among women and the third in terms of mortality. The Moroccan Health Ministry introduced the Human Papillomavirus vaccine to the national immunization program in October 2022.The study aims to evaluate the knowledge, the satisfaction level, and acceptability of HPV infection and vaccine among Moroccan medical students. We conducted a cross-sectional study from September 2021 to July 2022 among medical students above 5th year across the nine Moroccan medical universities. We shared our questionnaire through Google Forms. The descriptive data analysis was made through Google Forms and excel, and the analytic analysis was made using GraphPad Prism 8.0. We collected 636 answers. The mean age was 24.2 +/- 1.4 years old with a sex ratio (M/F) of 0.5. 3.3% (N=21) were vaccinated against HPV. The HPV infection knowledge mean score was 6.3 +/- 2 /11 (57.2% of good answers) and the vaccine knowledge mean score was 2.0 +/- 1,1 /5 (40% of good answers), with a training satisfaction rate of 7.3 +/- 2.6 /20 (36.5%). 85.8% of the participants (N= 546) were in favor of including the vaccine to the national immunization program. In conclusion, overall Moroccan medical students have an average knowledge of HPV infection and vaccine. The gap in HPV training should be filled especially in the era of the vaccine introduction. The majority of the students agree to make the vaccine mandatory, with superior rates than the other studies.

This study examines a case involving a 7-year-old child who developed dengue symptoms following Qdenga vaccination. Despite initial negative diagnostic results, molecular analysis confirmed an infection with DENV4. Next-generation sequencing detected viral RNA from both DENV2 and DENV4 serotypes, which were identified as vaccine-derived strains using specific primers. Phylogenetic analysis further confirmed that these sequences belonged to the Qdenga vaccine rather than circulating wild-type viruses. This case underscores the critical need for precise diagnostic interpretation in vaccinated individuals to avoid misdiagnosis and to strengthen public health surveillance. A comprehensive understanding of vaccine-induced viremia is essential for refining dengue surveillance, improving diagnostic accuracy, and informing public health strategies in endemic regions.

Background: Despite its global eradication in 1977, smallpox remains a concern owing to its potential as a biological agent, thereby prompting the ongoing development and utilization of its vaccine. Vaccination with the Vaccinia virus induces immunity against variola virus, the causative agent of smallpox; however, this immunity does not extend to viruses of different genera within the Poxviridae family. In this study, we aimed to assess the efficacy of an enzyme-linked immunosorbent assay (ELISA) method utilizing Vaccinia virus and recombinant A27L antigen for detecting antibodies against smallpox. Methods. Analysis of serum from 20 individuals pre- and post-vaccination with the CJ strain (CJ50300) revealed neutralizing antibodies, which were confirmed using the plaque reduction neutralization test (PRNT). The ELISA method, validated with a PRNT50 cut-off value of &gt;4, exhibited a sensitivity and specificity of &gt;95% and was particularly reactive with the inactivated virus. Furthermore, adherence to the smallpox vaccination policy revealed significant differences in Orthopoxvirus antibody levels among 300 individuals of different age groups. These findings highlight the reliability and efficacy of the ELISA method in detecting post-vaccination antibodies and contribute significantly to diagnostic methods to prepare for potential smallpox resurgence and bioterrorism threats.

Preventing COVID-19 in Gaza is crucial due to the devastation of advanced health services infrastructure by war. Despite the high protection offered by COVID-19 vaccines against severe disease, a 2021 survey in Gaza found only half of the population vaccinated and one-third vaccine hesitant. This follow-up study conducted in March 2023 aimed to re-evaluate vaccination levels, hesitancy, exposure to vaccine promotion efforts, and other risk factors in Gaza. A community-based cross-sectional survey with multistage stratified sampling was used. Associations of primary exposures and other determinants with vaccine status and hesitancy were quantified using bivariate and multivariate logistic regression. In 2023, 63.5% of adults received at least one vaccine dose compared to 49.1% in 2021. Vaccine hesitancy prevalence was 31.7% in 2023 versus 34.1% in 2021 (p=0.395). Adjusted odds of vaccination were 4.2 times higher among those referred by health workers compared to those not referred. Adjusted odds of vaccine hesitancy among those who received information on the vaccine from health workers were 0.3 times that of people who did not receive information. Results suggest health workers could play a crucial role in future vaccination strategies, as their vaccine promotion efforts were linked to better vaccine outcomes. Investing in the skills development of community health workers to contribute to these efforts is recommended.

In 2023, approximately 108 million infants worldwide received three doses of the diphtheria-tetanus-pertussis (DTP) vaccine, yet significant disparities persist, particularly in low-resource settings like West Africa. Despite the DPT vaccine's proven efficacy against diphtheria, the region continues to experience high rates of outbreaks for diphtheria, tetanus, and typhoid in 2024. This review aims to highlight the recent diphtheria crisis and analyze the trends and challenges of DTP vaccine coverage in West Africa by shedding light on socio-economic conditions, healthcare facilities and genetic factors. The review seeks to provide insights into improving vaccination rates and public health outcomes in the region, emphasizing the critical role of the DPT vaccine in combating life-threatening diseases. Enhanced surveillance and effective response strategies and development of region specific theraputics by the analysis of genomic variability in Africans, specifically within the human leukocyte antigen (HLA) locus are essential to address the ongoing public health challenges posed by diphtheria and related infections in West Africa.

Since its conception with the smallpox vaccination, worldwide-used vaccines have thwarted multiple pandemics including the recent COVID-19 outbreak. Insightful studies uncovered complexities of different functional networks of CD4 T cells [T helper 1 (Th1); Th2, Th17] and CD8 T cells (T cytotoxic; Tc) as well as B cells (BIgM, BIgG, BIgA and BIgE) subsets during response to vaccination. Both T and B cell subsets forge central, peripheral and tissue-resident subsets during vaccination. It also became apparent that each vaccination formed the network of T regulatory subsets, namely CD4+CD25+Foxp3+ T regulatory (Treg) cells and interleukin-10 (IL-10)-producing CD4+Foxp3− T regulatory 1 (Tr1) as well as many others, are shaping the quality/quantity of vaccine-specific IgM, IgG, and IgA antibody production. These components are especially critical for immunocompromised patients, such as older individuals and allograft recipients, as their vaccination may be ineffective or less effective. This review focuses on presenting how pre- and post-vaccination Treg/Tr1 levels influence the vaccination efficacy. Experimental and clinical work revealed that the Treg/Tr1 involvement evoked different immune mechanisms in diminishing vaccine-induced cellular/humoral responses. Alternative steps may be considered to improve the vaccination response by increasing a dose, changing the delivery route and/or repeated booster doses of vaccines. Vaccination may be combined with anti-CD25 (IL-2Ra chain) or anti-PD-1 (programmed cell death protein) monoclonal antibody (mAb) to decrease Tregs and boost the T/B cell immune response. All these data and strategies for immunizations are presented and discussed, aiming to improve the efficacy of vaccination in humans and especially in immunocompromised and older individuals as well as organ transplant patients.

Vaccine hesitancy has emerged as a significant barrier to achieving herd immunity and protecting populations from preventable diseases. Despite the proven effectiveness and safety of vaccines, many individuals remain hesitant or refuse to vaccinate themselves or their children. This review aims to identify the factors contributing to vaccine hesitancy, including misinformation, lack of trust in authorities, cultural beliefs, and access barriers. We also discuss the impact of vaccine hesitancy on public health, including outbreaks of vaccine-preventable diseases and erosion of trust in public health authorities. Furthermore, we present evidence-based communication strategies for addressing vaccine hesitancy, including building trust, providing accurate information, addressing myths and misconceptions, engaging with local influencers, and utilizing social media and digital platforms. By understanding the factors contributing to vaccine hesitancy and implementing effective communication strategies, healthcare providers, public health officials, and community leaders can work towards promoting widespread vaccine acceptance and protecting public health.

The evolution of the H5 highly pathogenic avian influenza (HPAI) viruses has led to the emergence of distinct groups with genetically similar clusters of hemagglutinin (HA) sequences. In this study, a consensus H5 HA sequence was cloned into the baculovirus expression system. The HA protein was expressed in baculovirus-infected insect cells and utilized as the antigen for the production of an oil emulsion-based H5 avian influenza vaccine (rBacH5Con5Mut). 21-day old SPF chickens were immunized with this vaccine and then challenged at 21 days post-vaccination (dpv) with clade 2.3.2.1, clade 2.3.4.4 and clade 7.2 of H5 HPAI virus, respectively. The chicken sera of vaccinated chickens exhibited high hemagglutination inhibition (HI) titers against the rBacH5 vaccine antigen, while lower HI titers were observed against the different challenge virus H5 hemagglutinins. Furthermore, the rBacH5Con5Mut vaccine provided 100% protection from mortality and clinical signs. Virus isolation results showed that oropharyngeal and cloacal shedding was prevented in 100% of the vaccinated chickens when challenged with clade 2.3.2.1 and clade 2.3.4.4 H5 viruses. When the rBacH5Con5Mut vaccine candidate was administrated at one day of age, 100% protection was demonstrated against challenge of clade 2.3.4.4 virus at 3 weeks of age, indicating the potential of this vaccine for hatchery vaccination. Overall, the rBacH5Con5Mut vaccine candidate with a consensus HA antigen and a single dose can protect chickens against different clades of H5 HPAI viruses throughout the rearing period of broiler chickens without a boost, thus fulfilling the criteria for an efficacious broad-spectrum H5 avian influenza vaccine.

Rubella infection is typically mild or asymptomatic except when infection occurs during pregnancy. Infection in early pregnancy can cause miscarriage, stillbirth, or congenital rubella syndrome. Only individuals that are still susceptible to rubella infection during child-bearing age are vulnerable to this burden. Rubella containing vaccine (RCV) is safe and effective, providing life-long immunity. However, average age-at-infection increases with increasing vaccination coverage, which could potentially lead to increased disease burden as well, if the absolute risk of infection during child-bearing age increases. Dynamics of rubella transmission were explored using EMOD, a software tool for building stochastic, agent-based infection models. Simulations of pre-vaccine, endemic transmission of rubella virus introduced RCV at varying levels of coverage to determine the expected future trajectories of disease burden. Introducing RCV reduces both rubella virus transmission and disease burden for a period of around 15 years. Increased disease burden is only possible more than a decade post-introduction, and only for contexts with low current burden and high transmission intensity. Low or declining rubella virus transmission intensity is concurrently associated with both greater disease burden and greater vaccine effectiveness. The risk of increasing burden through vaccination only exists for locations with persistently high infectivity, high connectivity, and high fertility. A trade-off between the risk of a small, future burden increase and a large, immediate burden decrease strongly favors RCV introduction.

In spite of prevalence gaps in several micronutrients supporting immune function, significance of their deficits/supplementation for efficacy of vaccines is underinvestigated. Thus, influence of supplementation combining vitamins C and D, zinc, selenium and manganese, and N-acetyl-cysteine on mouse IgG responses and underlying mechanisms to seasonal quadrivalent influenza vaccine (QIV) was investigated. QIV was given in two doses (28 days apart). The supplementation starting 5 days before the first injection increased the total serum IgG titre, through stimulation of germinal centre (GC) reaction in secondary lymphoid organs (SLOs), as indicated by increase in the frequency of GC B cells and follicular CD4+ T helper (Th) cells, and IL-21-producing Th cells. Additionally, the supplementation “optimized” IgG response following the second QIV injection by supporting more favorable (in respect to virus clearance) IgG2a response through favoring Th1 differentiation as indicating by Th1 (INF-γ) /Th2 (IL-4) signature cytokine level ratio upon QIV restimulation in SLO cell cultures. This most likely reflected partly their antioxidant action (as indicated by redox status analyses) on Th cell differentiation. Thus, the study forms solid base for further research aimed at repurposing use this safe and inexpensive micronutrient combination as an adjuvant for virus influenza vaccine.

The development of effective vaccines against SARS-CoV-2 remains a critical challenge amidst the ongoing global pandemic. This study introduces a novel approach to enhance mRNA vaccine efficacy by leveraging the untranslated region (UTR) of TMSB10, a gene identified for its significant mRNA abundance in antigen-presenting cells. Utilizing the GEO database, we identified TMSB10 among nine genes with the highest mRNA abundance in dendritic cell subtypes. Subsequent experiments revealed that TMSB10's UTR significantly enhances the expression of a reporter gene in both antigen-presenting and 293T cells, surpassing other candidates and a previously optimized natural UTR. Comparative analysis demonstrated that TMSB10 UTR not only facilitated higher reporter gene expression in vitro but also showed marked superiority in vivo, leading to enhanced specific humoral and cellular immune responses against the SARS-CoV-2 Delta variant RBD antigen. Specifically, vaccines incorporating TMSB10 UTR induced significantly higher levels of specific IgG antibodies and promoted a robust T-cell immune response, characterized by increased secretion of IFN-γ and IL-4 and the proliferation of CD4+ and CD8+ T cells. These findings underscore the potential of TMSB10 UTR as a strategic component in mRNA vaccine design, offering a promising avenue to bolster vaccine-induced immunity against SARS-CoV-2 and potentially other pathogens.

Background: Vaccinating children against COVID-19 is an essential public health approach for preventing infection in children and adults. This study aimed to explore parents' attitudes toward and the rate of COVID-19 vaccine hesitancy among children in Oman. Methods: This cross-sectional study used an online, self-administered questionnaire. The 9-item questionnaire was validated earlier and administered between June 2021 and May 2022. Multiple logistic regression was used to determine the factors associated with vaccine hesitancy. The parents received a pre-validated Google questionnaire. Responses from the parents of children younger than 11 years of age were accepted. Results: 384 participants completed the questionnaire, including 207 males (54%). The response rate was 86% (384/447). Of the 384 participants, 69% of the parents hesitated to vaccinate their children aged 1-11-year-old children). In parents of children aged 1–4 years, parental vaccination status was significantly associated with vaccine hesitancy (odds ratio [OR]: 0.116, 95% confidence interval [CI]: 0.044–0.306; p < 0.001). Additionally, vaccine hesitancy was significantly more common in mothers than in fathers (OR: 0.451, 95% CI: 0.240–0.848; p = 0.013). . Mothers of children were 77% more likely to be hesitant than fathers (.78, 95% confidence intervals (CI) = 0.50–0.1.23; p = 0.283). Conclusion: Many parents hesitated to vaccinate their children against COVID-19. Consequently, future awareness campaigns and strategies should target new vaccines. The results of our study show that the Arabic version of the 5-point Likert Scale for Vaccination Hesitancy is a valid and reliable tool.

Mucosal vaccines can target specific mucosal surfaces, such as the respiratory, genital, or intestinal mucosa. Conventional systemic immunization, such as intramuscular injections, do not provide mucosal immunity, including IgA, nor do they prevent pathogens from entering the mucous membranes. Nasal immunization protects mucosal membranes, but nasal antigen presentation appears to entail adjuvant to stimulate immunogenicity. Current treatments for mucosal diseases such as inflammatory bowel disease (IBD) and allergic dermatitis only aimed to temporarily relieve symptoms. Moreover, these treatments not only have drug resistance or side effects, but the disease can recur, leading to switching to other treatments. Therefore, there is a need to develop safe and effective treatments that provide better long-term outcomes to reduce the risk of recurrence. Regulatory T (Treg) cells have been used to suppress inflammation. To find advances in mucosal treatment, we investigated the therapeutic effects of intranasal pep27 mutant immunization. Here, a new method of Treg induction through intranasal immunization without adjuvant has been developed to potentially overcome allergies and mucosal inflammation of the lung-gut axis in animal models. The implementation of the pep27 mutant for these therapies should be preceded by studies of Treg resilience through clinical translational studies of dietary changes.

Infant hepatitis B vaccine coverage in China is high, with over 95% of infants immunized; however, high vaccine coverage can often mask low timeliness. The vaccination interval between the second and third dose is not clearly defined by immunization guidelines in China. This retrospective cohort study assessed the time interval distribution of hepatitis B vaccination among a cohort of randomly selected live births from Centers for Disease Control and Prevention across four provinces or municipalities in China between January 2017 and December 2021. Among the infants analyzed, 163,224 received the first dose of hepatitis B vaccine with 146,905 (90.0%) and 135,757 (83.2%) infants receiving the second and third doses, respectively. A total of 132,577 (90.2%) infants received the second dose between 28–61 days after the first dose. Of the 119,437 (88.0%) infants that completed the hepatitis B series between 61–214 days after the second dose, 87,067 (64.1%) infants were vaccinated with the third dose between 151–180 days after the second dose. The time interval distribution for the three doses of hepatitis B vaccine varied across the four provinces or municipalities (P&lt;0.001). Of the 58,077 infants who completed the hepatitis B vaccine series, 36,377 (62.6%) infants used the same type of hepatitis B vaccine for all three doses. Overall, the timeliness of hepatitis B vaccination for infants was lower than expected, with regional disparities observed. This highlights the need for improved timeliness through the introduction of a defined timeframe for the last two doses of vaccine, and training for obstetricians and related personnel.

Background: COVID-19 caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has become a recurrent endemic disease affecting the whole world. Since November 2021, Omicron and its subvariants are dominating. In order to prevent severe courses of disease, vaccines are needed to boost and maintain antibody levels capable of neutralizing Omicron. Recently we produced and characterized a SARS-CoV-2 vaccine based on a recombinant fusion protein consisting of hepatitis B virus (HBV)-derived PreS and two SARS-CoV-2 wild-type RBDs. Objectives: To develop a PreS-RBD vaccine which induces high levels of Omicron-specific neutralizing antibodies. Methods: We designed, produced, characterized and compared strain-specific (wild-type: W-PreS-W; Omicron: O-PreS-O), bivalent (mix of W-PreS-W and O-PreS-O) and chimeric (i.e., W-PreS-O) SARS-CoV-2 protein subunit vaccines. Immunogens were characterized in vitro by protein chemical methods, mass-spectrometry, circular dichroism in combination with thermal denaturation and immunological methods. In addition, BALB/c mice were immunized with aluminum hydroxide-adsorbed proteins and aluminum hydroxide alone (i.e., placebo) to study specific antibody and cytokine responses, safety and Omicron neutralization. Results: Defined and pure immunogens could be produced in large amounts as secreted and folded proteins in mammalian cells. Antibodies induced after vaccination with different doses of strain-specific, bivalent and chimeric PreS-RBD fusion proteins reacted with wild-type and Omicron RBD in a dose-dependent manner and resulted in a mixed Th1/Th2 immune response. Interestingly, RBD-specific IgG levels induced by the different vaccines were comparable but the W-PreS-O-induced virus neutralization titers against Omicron (median VNT50: 5000) were 7- and 2-fold higher than the W-PreS-W- and O-PreS-O-specific ones, respectively and 6-fold higher than those of the bivalent vaccine. Conclusion: Among the tested immunogens, the chimeric PreS-RBD subunit vaccine, W-PreS-O, induced the highest neutralizing antibody titers against Omicron. Thus, W-PreS-O seems to be a highly promising COVID-19 vaccine candidate for further preclinical and clinical evaluation.

Background: To describe the effectiveness and safety of COVID-19 vaccine in a series of patients with rheumatoid arthritis (RA). Methods: Retrospective single-center study of RA patients, fulfilling the ACR 1987 or ACR/EULAR 2010 classification criteria, that received first COVID-19 vaccine between December 2020 and October 2021, had post-vaccination serology and subsequent follow-up of at least 6 months in a university hospital. Vaccine effectiveness was evaluated by the serological response and the incidence of post-vaccine COVID-19, and safety by the incidence of adverse events (AE) and RA flares. Adjusted logistic and linear multivariate regression analyses were carried out with Stata® to identify factors associated with vaccine response. Results: We included 118 patients with RA (87.2% women, age 65.4±11.6 years, evolution 12.0±9.6 years). 95.8% received complete vaccination schedule. Most patients (88.1%) developed adequate humoral immunogenicity, and the degree of serological response was significantly related to younger age and previous COVID-19 infection. After vaccination, 18.6% presented mild SARS-CoV-2 infection. Vaccine AE (19.5%) were mostly mild and inversely associated with age (OR 0.95). RA flares were anecdotal (1.7%) and inversely related to age (OR 0.95). Conclusion: Our results suggest that COVID-19 vaccine induces adequate humoral immunogenicity, with an acceptable safety profile in RA patients.

Antibody responses to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are multi-targeted and variable over time. Multiplex quantitative serological assays are needed to provide accurate and robust seropositivity data for establishment of serological signatures during vaccination and or infection. We describe here, validation and evaluation of an electro-chemiluminescence (ECL) based Mesoscale Discovery assays (MSD), for estimation of total and functional IgG to SARS-CoV-2 spike, nucleocapsid, and receptor binding (RBD) proteins in human serum samples to establish serological signatures of SARS-CoV-2 natural infection and breakthrough cases. The 9-PLEX assay was validated as per ICH, EMA and US FDA guidelines using a panel of sera samples including the NIBSC/WHO international reference panel (20/268). Assay demonstrated high specificity and selectivity in inhibition assays, wherein the homologous inhibition was more than 85% and heterologous inhibition was below 10 %. Assay also met predetermined acceptance criteria for precision (CV < 30 %), accuracy (70-130 %) and dilutional linearity. Method applicability to serological signatures was demonstrated using sera samples (N=45) representing vaccinated, infected and breakthrough cases. The method was able to establish distinct serological signatures and thus provide potential tool for seroprevalence of SARS-COV-2 during vaccination or infection.

Oral vaccines are highly envisaged for veterinary applications due to their convenience and ability to induce protective mucosal immunity as the first line of defense. The present investigation harnessed live-attenuated Salmonella Typhimurium to orally deliver novel expression vector systems containing the Cap and Rep genes from porcine circovirus type 2 (PCV2), a significant swine pathogen. The antigen expression by the vaccine candidates JOL2885 and JOL2886, comprising eukaryotic pJHL204 and pro-eukaryotic expression pJHL270 plasmids respectively, was confirmed by western blot and IFA. We evaluated their immunogenicity and protective efficacy through oral vaccination in a mouse model. This approach elicited both mucosal and systemic immunity against PCV2d. Oral administration of the candidates induced PCV2-specific sIgA, serum IgG antibodies, and neutralizing antibodies, resulting in reduced viral loads in the livers and lungs of PCV2d-challenged mice. T-lymphocyte proliferation and flow-cytometry assays confirmed enhanced cellular immune responses after oral inoculation. The synchronized elicitation of both Th1 and Th2 responses was also confirmed by enhanced expression of TNF-α, IFN-γ, IL-4, MHC-I, and MHC-II. Our findings highlight the effectiveness and safety of the constructs with an engineered-attenuated S. Typhimurium, suggesting its potential application as an oral PCV2 vaccine candidate.

Excessive use of antibiotics to control colibacillosis on poultry farms in Morocco contributes to the development of multiresistant avian pathogenic E. coli. Autogenous vaccines are an alternative to antibiotic usage; the main goal of this study was to assess the efficacy of this approach to control recurrent outbreaks of colibacillosis in a large broiler production flow. A tetravalent autogenous vaccine (serotypes O78, O88, O91, and O185) was produced from E. coli strains isolated from clinical lesions in breeding hens and used on two farms (65,000 breeding hens in total). On each farm, contemporaneous groups were included: groups vaccinated twice (12 and 18 weeks of age) and unvaccinated control groups. The performances of these flocks, as well as the performances of broilers hatched from these breeders (12 farms, over 600,000 broilers in total), were recorded. A significant reduction in lesion scores, mortality rate and a significant increase in the number of saleable day-old chicks were observed among vaccinated hens. In broilers, body weight at slaughter, lesion scores, food conversion ratio, mortality and condemnation rates were significantly improved. This is the first field observation of a lasting effect of breeder hens immunization with an autogenous vaccine against E. coli on their offspring.

Immunosuppressed kidney transplant (KT) recipients respond weaker to COVID-19 vaccination than immunocompetent individuals. We tested antiviral IgG response in 99 KT-recipients and 66 healthy volunteers who were vaccinated with mRNA-1273 Moderna or BNT162b2 Pfizer-BioNTech vaccines. A subgroup of participants had their peripheral blood leukocytes (PBLs) evaluated for the frequency of T helper 1 (Th1) cells producing IL-2, IFN-γ and/or TNF-α, and IL-10-producing T-regulatory 1 (Tr) cells. Among KT-recipients, 45.8% had anti-SARS-CoV-2 IgG compared to 74.1% of healthy volunteers (p=0.009); also, anti-viral IgG levels were lower in recipients than in volunteers (p=0.001). When defined as non-responders (≤2,000 U/ml IgG), Moderna’s group had 10.8% and Pfizer-BioNTech’s group had 34.3% of non-responders at 6 months (p=0.023); similarly, 15.7% and 31.3% non-responders were in Moderna and Pfizer-BioNTech groups at 12 months, respectively (p=0.067). There were no non-responders among controls. Healthy volunteers had higher Th1 levels than KT recipients, while Moderna produced higher Th1 response than Pfizer-BioNTech. In contrast, Pfizer-BioNTech vaccine induced higher Tr1 response than Moderna vaccine (p&lt;0.05); overall, IgG levels correlated with Th1(fTTNF-α)/Tr1(fTIL-10) ratios. We propose that the higher number of non-responders in Pfizer-BioNTech group than Moderna group was caused by more potent activity of regulatory Tr1 cells in KT-recipients vaccinated with Pfizer-BioNTech vaccine.

(1) Background: We previously reported the development of a recombinant protein SARS-CoV-2 vaccine, consisting of the Receptor-Binding Domain (RBD) of the SARS-CoV-2 spike protein, adjuvanted with aluminum hydroxide (alum) and CpG oligonucleotides. In mice and non-human primates, our wild-type (WT) RBD vaccine induced high neutralizing antibody titers against the WT isolate of the virus, and, with partners in India and Indonesia it was later developed into two closely resembling human vaccines, Corbevax and Indovac. Here, we describe the development and characterization of a next-generation vaccine adapted to the recently emerging XBB variants of SARS-CoV-2. (2) Methods: We conducted preclinical studies in mice using a novel yeast-produced SARS-CoV-2 XBB.1.5 RBD subunit vaccine candidate formulated with alum and CpG. We examined the neutralization profile of sera obtained from mice vaccinated twice intramuscularly at a 21-day interval with the XBB.1.5-based RBD vaccine, against WT, Beta, Delta, BA.4, BQ.1.1, BA.2.75.2, XBB.1.16, XBB.1.5 and EG.5.1 SARS-CoV-2 pseudoviruses. (3) Results: The XBB.1.5 RBD/CpG/alum vaccine elicited a robust antibody response in mice. Furthermore, serum from vaccinated mice demonstrated potent neutralization against the XBB.1.5 pseudovirus as well as several other Omicron pseudoviruses. However, regardless of high antibody cross-reactivity by ELISA, the anti-XBB.1.5 RBD antigen serum showed low neutralizing titers against the WT and Delta virus variants. (4) Conclusions: Whereas we observed modest cross-neutralization against Omicron subvariants by sera from mice vaccinated with the WT RBD/CpG/Alum vaccine or with the BA.4/5-based vaccine, sera raised against the XBB.1.5 RBD showed robust cross-neutralization. These findings underscore the imminent opportunity for an updated vaccine formulation utilizing the XBB.1.5 RBD antigen.

Due to their distinct physical, chemical, and biological characteristics, biopolymers, in particular Poly Ethylene Glycol (PEG) and Cellulose, are frequently used in biomedical medicine as drug or vaccine delivery systems. In this study, we have done a systematic review and a meta-analysis to compare current developments in many PEG and cellulose-based hydrogels, including double network hydrogels, injectable hydrogels, sliding hydrogels, conductive hydrogels, responsive hydrogels, and nanocomposite hydrogels. The pharmacokinetic properties, including physicochemical properties, biocompatibility, biodegradability, temperature, and pH, have been studied as these critical factors are to be considered for deciding the suitability of the drug for delivery. Moreover, the study has evaluated the controlled-release parameters such as half-life, circulation time, maximum release percentage of loaded drug released, burst release, maximum release, and drug-release kinetics. Finally, the efficacy and immune response of hydrogel was studied for future choice, including the cellulose hydrogel system in COVID-related long-term vaccine delivery. The finding revealed that cellulose-based hydrogel is effective for vaccine delivery.

Background: Understanding the distribution of HPV types in cervical cancer cases is crucial for evaluating the effectiveness of HPV screening and vaccination in reducing cervical cancer burden. This study aimed to assess genotype prevalence among 178 cervical cancer cases detected during a 20-year screening period in Northern Norway and compare the potential efficacy of HPV vaccines in preventing cervical cancer. Methods: A total of 181 formalin-fixed paraffin-embedded (FFPE) tissue samples from women diagnosed with cervical cancer between 1995 and 2015 in Troms and Finnmark, Norway, were analyzed using a 45-type HPV DNA test. The results were compared to a 7-type HPV mRNA test targeting oncogenic types included in the nonavalent HPV vaccine. Results: Invalid HPV test results were observed in 1.7% (3/181) of the samples and were subsequently excluded from further analysis. Among the remaining cases, 92.7% (165/178) tested positive for HPV using any test combination. HPV DNA was detected in 159 cases (89.3%), while HPV mRNA was detected in 149 cases (83.7%). The most prevalent HPV types were 16 and 18, responsible for 70.8% of the cases, with the nonavalent vaccine types accounting for 86.6% of cases. HPV 35 was identified in eight cases (4.5%). Conclusion: The bivalent/quadrivalent HPV vaccines have the potential to prevent 76.4% (126/165) of HPV-positive cervical cancer cases, while the nonavalent vaccine could prevent 93.3% (154/165) of cases. Tailoring screening strategies to target HPV types with the highest oncogenic potential may improve cervical cancer detection and enable targeted interventions for high-risk individuals. The use of a 7-type HPV mRNA test holds promises as an advantageous approach.

Hepatitis B is a potentially life-threatening infectious disease caused by the hepatitis B virus (HBV), which affects the liver. Every year, about 390,000 people die from HBV-related diseases in China, about 86 million people are carriers of HBV, accounting for about 6% of the total population, and 30 million people are chronically infected. From 2002 to 2007, though China government launched “The Global Alliance for Vaccines and Immunization (GAVI)” program to reduce HBV infection in children, but the number of hepatitis B cases in China remains high. Reasonable estimation of potential HBV carriers is crucial to prevention and control the spread hepatitis B virus. This study is based on the case data from the National Bureau of Statistics of China from 2003 to 2021. We build a dynamic model that includes potential hepatitis B virus carriers, use nonlinear least squares and genetic algorithms to fit the parameters in the model, and calculate the reproduction number of hepatitis B virus transmission in the population and obtain R_c=1.741. The number of potential hepatitis B virus carriers is estimated to be 449,535 (95%CI [415651 to 483420]) based on our model, which is 30.49% of the total number of hepatitis B cases, and the simulation results show the number of chronic hepatitis B incidence decreases as the vaccination rate α increases, increasing α by 20%, the number of chronic hepatitis B incidence decreases by 169,469 on average.

This paper proposes an imperfectly vaccinated SVEIR model for latent age. We calculate the equilibrium points and basic reproduction number of the model. The asymptotic smoothness, uniform persistence and the existence of the attractor of the semi-flow generated by the solutions of the system are addressed. Moreover, using LaSalle’s invariance set principle and constructing Volterra-type Lyapunov functions, we can prove the global asymptotic stability of both the disease-free equilibrium and the endemic equilibrium of the model. The conclusion is that if the basic reproduction number R0 is less than one, the disease will gradually disappear. On the other hand, if the number is greater than one, the disease will become endemic and persist. Finally, measures that can effectively control the ongoing transmission of the disease have been obtained.

Background: Routine human papillomavirus (HPV) vaccine uptake continues to be suboptimal since its recommendation in 2006 for girls and in 2011 for boys. This paper aims to review published quality improvement (QI) methodologies on interventions to improve HPV vaccine uptake among adolescents; Methods: Science Direct and Scopus databases were searched for QI initiatives evaluating the effect of multimodal interventions to improve HPV vaccination rates (initiation and/or completion of series) among adolescents. Studies that included an outcome of interest among adolescents aged 10 to 18 years old were included. Two investigators worked independently to screen for potential articles and a designated investigator extracted data on study characteristics and evaluated the outcomes; Results: Preliminary search yielded a total of 523 articles and 13 were included in the final analysis. Common strategies were provider-specific and patient- and/or parent-specific interventions, with an emphasis on education and knowledge empowerment. System-level interventions such as policy changes and revised protocol were less commonly prescribed despite being associated with more significant weight on the overall outcome; Conclusions: Creative, sustainable, and economical multilevel interventions that focus not only on provider training and public education but also incorporate local policy and system enhancement can substantially improve HPV vaccination coverage among adolescents.

Introduction: COVID-19 vaccines have been the most effective means in curbing the infection, however, vaccine hesitancy has been seen as a threat to global health. Objective: the study aimed to assess the prevalence and predictors of COVID-19 vaccine hesitancy among healthcare workers in infectious disease centers in Ghana. Method: A cross-sectional study and proportionate stratified sampling method was used to recruit participants from various infectious disease centers. Result: data from 170 participants were analyzed, revealing a low prevalence of COVID-19 vaccine hesitancy (11.2%) among healthcare workers. However, only 31.1% of the fully vaccinated participants had taken the booster dose. Factors such as concerns about vaccine safety and side effects from previous doses, indecisiveness, a lack of time to receive the vaccine and lack of access to accurate information, prefered natural immunity were the significant predictors of vaccine hesitancy among healthcare workers. Participants with good perception of the risk posed by COVID-19 was positively correlated with COVID-19 vaccine acceptance. Conclusion: the study suggests that policies should be enacted to ensure health workers are vaccinated against highly contagious infectious diseases to prevent their spread among the general population. Training and health promotion campaigns should also be organized to encourage healthcare workers to accept and patronize the vaccines.

In the wake of the Covid-19 crisis, a need has arisen to prevent and treat two related conditions, Covid vaccine injury and long Covid, both of which have a significant vascular component. Therefore, the management of these conditions require the development of strategies to prevent or dissolve blood clots and restore circulatory health. This review summarizes the evidence on strategies that can be applied to treat both long and vaccine injuries based on similar mechanisms of action.

The coronavirus disease (COVID-19) vaccine is key to reducing the probability of contracting COVID-19. The vaccine is generally known to prevent severe illness, death, and hospitalization as a result of the disease and for considerably reducing COVID-19 infection risk. Accordingly, this might significantly change an individual’s perceived risk of altering everyday behaviors. For instance, the proliferation of vaccination is anticipated to reduce preventive behaviors such as staying at home, handwashing, and wearing a mask. We corresponded with the same individuals monthly for 18 months from March 2020 (early stage of COVID-19) to September 2021 in Japan to independently construct large sample panel data (N=54,007), with a participation rate of 54.7 %. We used a fixed effects model, controlling for key confounders, to determine whether vaccination was associated with a change in preventive behaviors. The major findings are as follows. Contrary to the prediction, (1) based on the whole sample, being vaccinated against COVID-19 led people to stay at home; however, it did not change the habit of handwashing and wearing a mask. Especially after the second shot, respondents were likelier to stay at home by 0.107 (95% CIs: 0.059–0.154) points on a 5-point scale compared to before the vaccination. Dividing the entire sample into young and old, (2) those aged ≤ 40 years were more likely to go out after being vaccinated, and (3) people over 40 years of age were more likely to stay at home (similar to the first result). Preventive behaviors impact all individuals during the current pandemic. Informal social norms motivate people to increase or maintain preventive behaviors even after being vaccinated in societies where these behaviors are not enforced.

Abstract: Over the years, several distinct pathogenic coronaviruses have emerged, including the pandemic SARS-CoV-2 which is difficult to curtail despite the availability of licensed vaccines. The difficulty in managing SARS-CoV-2 is linked to changes in the variants’ proteins, especially in the spike protein (S) used for viral entry. These mutations, especially in the S, enable the virus to evade the immune responses induced by natural infection or vaccination. However, some parts of the SP in the S1 subunit and the S2 subunit are considered conserved among coronaviruses. In this review, we will discuss the epitopes in the SARS-CoV-2 S1 and S2 subunit proteins that have been demonstrated by various studies to be conserved among coronaviruses and may be immunogenic for the development of vaccine. Considering the higher conservancy of the S2, we will further discuss the likely challenges that could limit the S2 subunit from inducing robust immune responses and the promising approaches to increase their immunogenicity.

Vaccination attitudes among healthcare workers (HCWs) is a vital factor for measuring their level of vaccination uptake and intention to recommend vaccinations to their patients. To our knowledge, no study has been conducted in South Africa to assess hesitancy to influenza vaccines among HCWs. We used questionnaire adapted from Betsch and colleagues to conduct an online and face-to-face cross-sectional study among HCWs at the start of COVID-19 vaccine roll-out prior to the flu season. Main outcome was influenza vaccine hesitancy. We used multivariate logistic regression to assess predictors of influenza vaccine hesitancy. Of 401 participants, 64.5% were women, 49.2% nurses, and 12.5% physicians. A total of 54.9% were willing to accept vaccination, 20.4% were undecided, and 24.7% intended to refuse. Older participants above 17-25 years and physicians were likely to receive the vaccine. Key predictors of vaccine acceptance were confidence in the effectiveness, consideration of benefits and risks, and willingness to be vaccinated to protect others. Influenza vaccine hesitancy was highest in those who did not trust that influenza vaccines are safe. For future flu seasons, tailored education programs targeting younger HCWs and more information about the composition of flu vaccines would be vital to improve vaccine uptake.

The presence of a non-structural protein 1 (NS1) in tick-borne encephalitis (TBE) vaccines and the possible induction of an NS1-specific immune response in vaccinated individuals remains a somewhat controversial topic. Previously, we detected the presence of NS1 in Encepur TBE vaccine by mass spectrometry and found the induction of NS1-specific IgG antibodies in mice vaccinated with FSME-Immun TBE vaccine. Here, in this follow-up study, we examined the dynamics and extent of the NS1-specific IgG response in mice vaccinated with these two vaccines in more detail and compared it with the IgG response to the whole virus (WV). Mice were vaccinated at two-week intervals with a total of six doses of each vaccine, and levels of IgG antibodies to TBE virus WV and NS1 were measured by ELISA after each dose. Both vaccines elicited a robust anti-WV IgG response after two doses. The Encepur vaccine did not elicit NS1-specific IgG even after all six doses. In contrast, FSME-Immun vaccine triggered production of NS1-specific IgG after four doses. The results indicate that FSME-Immun is the only vaccine that elicits an NS1-specific antibody response in mice. However, compared to WV-specific IgG, the NS1-specific response is weaker, and a higher number of doses is required to induce detectable levels of NS1-specific IgG antibodies.

The incidence and mortality rates of cervical cancer are rising among young women in Japan. In November 2021, the Japanese Ministry of Health, Labour and Welfare reinstated the active recommendation for the human papillomavirus (HPV) vaccine, which was discontinued in June 2013 due to reports of adverse reactions, including chronic pain and motor dysfunction, following vaccination. However, vaccine hesitancy among the younger generation remains, and it is essential to identify the barriers in vaccination uptake. Therefore, we aim to conduct a randomized study using different methods of providing educational contents to improve health literacy regarding cervical cancer and HPV vaccination among female students in Japan. Here, we present the results of our preliminary report and discuss current topics related to HPV vaccination in Japan. Data were collected from 27 female students—divided into three groups: no intervention, print-based intervention, and SNS-based intervention—using the Health Literacy Scale and Communicative and Critical Health Literacy scale. Our primary results indicate that participants’ knowledge and health literacy improved post intervention. Therefore, medical professionals must provide accurate scientific knowledge regarding routine HPV vaccination and the risk of cervical cancer to young women to improve their health literacy and subsequently increase the HPV vaccination rates.

Mosquitoes conveying Plasmodium store parasites into the skin of the mammalian host. Parasites make a trip through the circulation system to the liver, where they cross a few hepatocytes prior to building up a disease. Inside the last hepatocyte the parasite goes through morphogenesis and afterward abiogenetically partitions to become more than 20,000 blood-infective parasites, called merozoites. On account of P. vivax, P. ovale, and P. cynomolgi, the parasites can stay lethargic in the liver in structures called hypnozoites. The merozoites are delivered once again into the circulation system, where they start the repetitive blood stage. Inside erythrocytes, a little division of parasites separate into male or female gametocytes. These gametocytes are ingested by the mosquito during blood taking care of, where they will duplicate explicitly, in the long run prompting the arrangement of sporozoites

Allergic diseases represent a global health and economic burden of increasing significance. The lack of disease-modifying therapies besides specific allergen immunotherapy (AIT) which is not available for all types of allergies, necessitates the study of novel therapeutic approaches. Exosomes are small endosome-derived vesicles delivering cargo between cells and thus allowing inter-cellular communication. Since immune cells make use of exosomes to boost, deviate, or suppress immune responses, exosomes are intriguing candidates for immunotherapy. Here, we review the role of exosomes in allergic sensitization and inflammation and we discuss the mechanisms by which exosomes could be used in immunotherapeutic approaches for the treatment of allergic diseases. We propose the following approaches: a) Mast cell derived exosomes expressing IgE receptor FcεRI could absorb IgE and down-regulate systemic IgE levels. b) Tolerogenic exosomes could suppress allergic immune responses via induction of regulatory T cells. c) Exosomes could promote TH1-like responses towards an allergen. d) Exosomes could modulate IgE-facilitated antigen presentation.

Live attenuated influenza virus (LAIV) vaccines elicit a combination of systemic and mucosal immunity by mimicking a natural infection. To further enhance protective mucosal responses, we incorporated the gene encoding the IgA-inducing protein (IGIP) into the LAIV genomes of the cold-adapted A/Leningrad/134/17/57 (H2N2) strain (caLen) and the experimental attenuated backbone A/turkey/Ohio/313053/04 (H3N2) (OH/04att). Incorporation of IGIP into the caLen background led to a virus that grew poorly in prototypical substrates. In contrast, IGIP in the OH/04att background (IGIP-H1att) virus grew to titers comparable to the isogenic backbone H1att (H1N1) without IGIP. IGIP-H1att- and H1caLen-vaccinated mice were protected against lethal challenge with a homologous virus. The IGIP-H1att vaccine generated robust serum HAI responses in naïve mice against the homologous virus, equal or better than those obtained with the H1caLen vaccine. Analyses of IgG and IgA responses using a protein microarray revealed qualitative differences in humoral and mucosal responses between vaccine groups. Overall, serum and bronchoalveolar lavage samples from the IGIP-H1att group showed trends towards increased stimulation of IgG and IgA responses compared to H1caLen samples. In summary, introduction of genes encoding immunomodulatory functions into a candidate LAIV that can serve as natural adjuvants to improve overall vaccine safety and efficacy.

Seasonal influenza is a common cause of hospital admission, especially in older people and those with comorbidities. The objective of this study was to determine influenza vaccine effectiveness (VE) in preventing intensive care admissions and shortening the length of stay (LOS) in hospitalized laboratory-confirmed influenza cases (HLCI) in Catalonia (Spain).A retrospective cohort study was carried out during the 2017-2018 season in HLCI aged ≥ 18 years from 14 public hospitals. Differences in means and proportions were assessed using a t-test or a chi-square test as necessary and the differences were quantified using standardized effect measures; Cohen’s d for quantitative and Cohen’s w for categorical variables. Adjusted influenza vaccine effectiveness in preventing severity was estimated by multivariate logistic regression where the adjusted VE = (1-adjusted odds ratio) ·100%; adjustment was also made using the propensity score.We analyzed 1414 HLCI aged ≥ 18 years; 465 (33%) were vaccinated, of whom 437 (94%) were aged ≥ 60 years, 269 (57.8%) were male and 295 (63.4%) were positive for influenza type B. ICU admission was required in 214 (15.1%) cases. There were 141/1118 (12.6%) ICU admissions in patients aged ≥ 60 years and 73/296 (24.7%) in those aged < 60 years (p<0.001). The mean LOS and ICU LOS did not differ significantly between vaccinated and unvaccinated patients. There were 52/465 (11.2%) in vaccinated cases) ICU admissions in vaccinated cases vs. 162/949 (17.1%) in unvaccinated cases. Patients admitted to the ICU had a longer hospital LOS (mean: 22.4 [SD 20.3] days) than those who were not (mean: 11.1 [SD14.4] days); p<0.001. Overall, vaccination was associated with a lower risk of ICU admission. Taking virus types A and B together, the estimated adjusted VE in preventing ICU admission was 31% (95% CI 1-52; p=0.04). When stratified by viral type, the aVE was 40% for type A (95% CI -11-68; p = 0.09) and 25% for type B (95% CI -18-52; p = 0.21). Annual influenza vaccination may prevent ICU admission in cases of HLCI. A non-significantly shorter mean hospital stay was observed in vaccinated cases. Our results support the need to increase vaccination uptake and public perception of the benefits of influenza vaccination in groups at a higher risk of hospitalization and severe outcomes.

The COVID-19 pandemic is a devastating blow to the entire world community and changes the order of human life. All efforts and strategies are being carried out to contain and reduce the spread of the SARS-COV-2 virus, both by tightening the health protocol and using vaccines to the public. Currently, several vaccines are available and have passed phase 3 clinical trials, such as vector vaccines (Gamaleya Sputnik V Russia, University of Oxford/AstraZeneca, CanSino, and Janssen Pharmaceutical Companies), mRNA-based vaccines (Moderna/BioNTech/Fosun Pharma/Pfizer), inactivated vaccines (SinoVac and SinoPharm from China, Covaxin from Bharat Biotech India), and adjuvanted recombinant protein nanoparticles (Novavax from the USA) are expected to be able to suppress the spread of the virus and produce a minimum of 70 percent herd-immunity in a population. Each vaccine's efficacy varies from the lowest, namely the Sinovac vaccine (CoronaVac) 50% to the highest the Novavax vaccine (NVX-Cov2373) 96% effectivity value. Moreover, further rigorous research is still being carried out for the development of an effective and efficient vaccine.

The role of T cell immunity has been acknowledged in recent vaccine development and evaluation. We tested the humoral and cellular immune responses to Flucelvax®, a quadrivalent inactivated seasonal influenza vaccine containing two influenza A (H1N1 Singapore/GP1908/2015 IVR-180 and H3N2 North Carolina/04/2016) and two influenza B (Iowa/06/2017 and Singapore/INFTT-16-0610/2016) virus strains, using peripheral blood mononuclear cells stimulated by pools of peptides overlapping all the individual influenza viral protein components. Baseline reactivity was detected against all four strains both at the level of CD4 and CD8 responses and targeting different proteins. CD4 T cell reactivity was mostly directed to HA/NA proteins in influenza B strains, and NP/M1/M2/NS1/NEP proteins in the case of the Influenza A strains. CD8 responses to both influenza A and B viruses preferentially targeted the more conserved core viral proteins. Following vaccination, both CD4 and CD8 responses against the various influenza antigens were increased in day 15 to day 91 post vaccination period and maintained a Th1 polarized profile. Importantly, no vaccine interference was detected, with the increased responses balanced across all 4 included viral strains for both CD4 and CD8 T cells, and targeting HA and multiple additional viral antigens.

Introduction: The SARS-CoV-2/COVID-19 pandemic has triggered the need for developing rapidly effective and safety vaccines to prevent infection, particularly in those at-risk populations such as medical personnel. The objective of this study was to assess perception of COVID-19 vaccination amongst Colombian physicians featuring two different sceneries of COVID-19 vaccination. Methods: A cross-sectional analytical study was carried out through an online survey, directed at medical staff in several cities in Colombia. The percentage of physicians who have a positive perception to be vaccinated and the associated factors that determine that decision were determined. A binomial regression analysis adjusted for age and sex was carried out, taking as a dependent variable the acceptance of free vaccination with an effectiveness of 60 and 80%. The most significant factors were determined in the non-acceptance of vaccination. Results: Between 77.1% and 90.8% of physicians in Colombia, accept COVID-19 vaccination, according to the scenario evaluated where the effectiveness of the vaccine was 60 or 80%, respectively. Medical specialty, have ever paid for a vaccine, recommend administrating the vaccine to their parents or people over 70 years and dispense the vaccine to their children were the factors to be vaccinated for free with an effectiveness of 60% and 80%. Conclusions: There is a high perception of the intention to vaccinate physicians in Colombia against COVID-19. But it is very similar to that of the general population, according to results reported in other studies.

Background: Renewed measles outbreaks in recent years indicate that despite the routine availability of vaccines for a disease that is considered contagious, dangerous and deadly, many anti-vaccinationists do not vaccinate their children, which consequently endangers public health. This study aimed to investigate the factors that influence mothers to vaccinate their children, and whether the Health Belief Model (HBM) could predict compliance or non-compliance. Methods: This was a quantitative correlational research, utilizing a 40-item questionnaire administered to 181 mothers in Israel. Results: The findings indicated two main factors that affected mothers' intention to vaccinate their children against measles: first, their perception of the vaccine's advantages, and second, their perception of the severity of the disease. It was also found that the HBM variables significantly affected the intention to administer vaccines. Conclusion: Consequently, raising public awareness of the vaccine's advantages and importance to preventing mass infection, as well as attempts by the health system and practitioners to understand the motivations of anti-vaccinationists (including health beliefs and cultural sensitivities) could significantly increase the percentage of vaccinated children, and eradicate the measles epidemic.

Knowing the “point of view” of the immune system is essential to understand the characteristic of a pandemic, such as that generated by the Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV)-2, responsible for the Coronavirus Disease (COVID)-19. In this review, we will discuss the general host/pathogen interactions dictating protective immune response or immunopathology, addressing the role of immunity or immunopathology in influencing the clinical infection outcome, and debate the potential immunoprophylactic and immunotherapy strategies required to fight the virus infection.

The Covid-19 infodemic can be countered by scientific evidences, clear and consistent communication and improved health literacy of both individuals in need of information and those providing it. A rapid online survey was carried out to evaluate vaccine literacy (VL) skills in the general population and perceptions about candidate Covid-19 vaccines, as well as behavior and beliefs about current vaccinations. Observed VL levels were sufficiently high and consistent with previous observations - where comparable self-reported tools were administered face-to-face and paper-and-pencil - the mean functional score being =2.92, while the interactive-critical one was =3.27, on a maximum of 4. Perceptions regarding future Covid-19 vaccines, along with beliefs about vaccination, were mostly positive and significantly associated with functional and interactive-critical VL scales. Despite obvious limitations, the study confirms that rapid surveys via web are a suitable method to evaluate and trail attitudes during infectious disease outbreaks, and to assess health literacy skills about vaccination, which can be useful to adapt medical communication strategies, for a better understanding of the value of immunization.