Objective: Meningococcal meningitis (MM) is an acute, severe respiratory infectious disease caused by Neisseria meningitidis and remains an important cause of morbidity/mortality in children. Immunization with meningococcal vaccine (MV) is the most effective measure to control and prevent the transmission of MM. In this study, in order to support the appropriate use of various MVs in the prevention of MM, the effects of MVs, especially single-dose and inter-booster administered, on inflammatory parameters in

Background: The rise of new SARS-CoV-2 mutations brought challenges and progress in the global fight against COVID-19. Mutations in spike and accessory genes affect transmission, vaccine efficacy, treatments, testing, and public health strategies. Monitoring emerging variants is crucial to halt virus spread. Methods: 44 nasopharyngeal/oropharyngeal swabs from Kenyan patients were sequenced with the Illumina platform. Galaxy's bioinformatic tools were used for genomic analysis. SARS-CoV-2 genome classification was done using PANGOLIN and mutation annotation with the COVID-19 Annotator tool. Results: The study showed 5 clades to be circulating in the region. 38(86%) were BA.1.1; 2(5%) were BA.1.1.1; 1(2%) was BA.1; 1(2%) was BA.1.14 and 2(5%) were AY.46. These clades had a cumulative of 173 mutations among them with 50 novel mutations. Forty-eight of these novel mutations occurred in a low frequency of 2.3% of the sequences tested while the other two, S:R214R, and NSP2:A555A, were for 43.2% and 18.2% of the cases respectively. Conclusions: The high-frequency novel mutations were synonymous mutations, a phenomenon that was previously viewed as phenotypically silent but recent studies indicate they can affect viral fitness with potential functional associations. These findings add to the understanding of the SARS-CoV-2 virus future evolutionary and immunological dynamics in the region

This study evaluates the incidence and characteristics of adverse events (AEs) following the second COVID-19 booster dose, leveraging Taiwan's distinctive approach of extending booster vaccinations to all citizens, unlike the targeted high-risk group strategies in other countries. Utilizing data from Taipei Veterans General Hospital's Vaccine Adverse Event Reporting System (VAERS) from October 27, 2022, to January 19, 2023, the research examines AEs in 441 out of 1711 second booster recipients, considering factors like age, vaccine brands, and booster combinations. The findings reveal incidence rates (IR) of 25.6% (95% CI: 21.1-30.8) after the first booster and 24.9% (95% CI: 20.5-30.0) after the second, mostly non-serious, with those having AEs post-first booster 5 times more likely to report them again (Incidence rat rato, 5.02, P<0.001). Significantly, switching from the mRNA1273 vaccine to another brand reduced AE risk by 18%. The study underscores that AEs are more repetitive than cumulative with additional booster doses, advocating for personalized vaccination strategies based on individual medical histories and previous vaccine reactions. These insights are valuable for healthcare providers in discussing potential AEs with patients, thereby improving vaccine compliance and public trust, and for policymakers in planning future booster vaccination strategies.

Recently, Mulroney,et.al., demonstrated that Pfizer’s ModRNA Covid vaccine, but not AstraZeneca Covid vaccine, produce aberrant foreign proteins in vivo due to reading frame shift in ribosomes. This phenomenon could elucidate the notable surge in autoimmune diseases following the administration of ModRNA vaccines compared to Influenza vaccines between 2020 and 2023, as found in the VAERS database. These findings bear significant implications for the future application of mRNA technology, emphasizing the necessity of modifying the design of the mRNA sequence to mitigate these defects. Remarkably, Mulroney and collaborators achieved a reduction in frame shift proteins by introducing additional edits to the mRNA sequences. This adjustment is pivotal for rectifying the flawed design of the ModRNA employed by Pfizer. In light of these findings, many advocate for the immediate recall and further investigation of these products. The notion of a "future mRNA-based therapy" should be postponed indefinitely.

Co-delivery of antigens and adjuvants to the same antigen presenting cells (APCs) can significantly improve the efficacy and safety profiles of vaccines. Here, we report amine-grafted silica nanoparticles (A-SNPs) as a tunable vaccine co-delivery platform for TLR7/8 agonists along with the recombinant influenza antigen hemagglutinin H7 (H7) to APCs. A-SNPs of two different sizes (50 and 200 nm) were prepared and coated with INI-4001 at different coating densities, followed by co-adsorption of H7. Both INI-4001 and H7 showed > 90% adsorption to the tested A-SNP formulations. TNF-α and IFN-α cytokine release by human peripheral blood mononuclear cells as well as TNF-α, IL-6, and IL-12 release by mouse bone marrow-derived dendritic cells revealed that the potency of the INI-4001-adsorbed A-SNPs (INI-4001/A-SNP) formulations can be improved relative to aqueous formulation control. This improved potency was dependent on particle size and ligand coating density. In addition, slow-release profiles of INI-4001 were measured from INI-4001/A-SNP formulations in plasma with 30-50% INI-4001 released after 7 days. In vivo murine immunization studies demonstrated significantly improved H7-specific humoral and Th1/Th17-polarized T cell immune responses with no observed adverse reactions. Low-density 50 nm INI-4001/A-SNP elicited significantly higher IFN-γ and IL-17 induction over that of the H7 antigen only group and INI-4001 aqueous formulation controls. In summary, this work introduces an effective and biocompatible SNP-based co-delivery platform that enhances the immunogenicity of TLR7/8 agonist-adjuvanted subunit influenza vaccines.

Malignant neoplasms arising from the gastrointestinal (GI) tract are among the most common cancer types with a high mortality rate. Despite advances in treatment in a small subgroup harboring targetable mutations, the outcome remains poor, accounting for one in three cancer-related deaths observed globally. As a promising therapeutic option in various tumor types, immunotherapy with immune checkpoint inhibitors has also been evaluated in GI cancer, albeit with limited efficacy except for a small subgroup expressing microsatellite instability. In the quest for more effective treatment options, energetic efforts have been placed to evaluate the role of several immunotherapy approaches comprising of cancer vaccines, adoptive cell therapies and immune checkpoint inhibitors. In this review, we report our experience with personalized dendritic cell cancer vaccine and cytokine-induced killer cell therapy in three patients with GI cancers and summarize current clinical data on combined immunotherapy strategies.

Background: Since 2000, vaccine coverage in Sub-Saharan Africa (SSA) has surpassed multiple milestones. Its contribution to global health, especially in low-middle-income countries is one of the achievements in global governance of modern medicine, averting 2-3 million child deaths every year. However, in Nigeria, vaccine-preventable-diseases still account for one in eight child deaths before their fifth-year birthday and remains one of the ten countries where 4.3 million children under five are without complete immunization. The reasons for declining childhood vaccine demand are unclear. Therefore, the goal of this contribution is to shed light on the reasons to set a foundation for future interventions. Methods: Four focus group discussions were conducted. The primary targets were mothers of children 0 – 12 months old in Nigeria. A simplified quota sampling approach was used to select mothers in four geographical clusters of Nigeria’s Federal Capital Territory. At least six mothers from each cluster were randomly included, giving a total of 24 participants. An interview guide developed from the 5C psychological antecedence model was used (assessing confidence, complacency, calculation, constraints, collective responsibility); two additional variables were included that had proved meaningful in previous work (religion and masculinity). The data were analyzed using meta-aggregation approach such as framework synthesis, which summarized data in a stepwise fashion. Results: The sample was generally relatively positive towards vaccination. Still, mothers reported low trust in vaccine safety and the healthcare system (confidence). Yet, they had great interest in seeking additional information during antenatal visits (calculation), difficulties in prioritizing vaccination over other equally competing priorities (constraints) and were aware that vaccination translates into overall community health and wellbeing (collective responsibility). They had a bias towards God as ultimate giver of good health (religion) and reported that their husbands played a dominant role in vaccination decision-making (masculinity). Mothers perceived their children vulnerable to disease outbreaks, which motivated them to get them vaccinated (complacency). Conclusion: The 5C model and the added determinants provided a useful qualitative tool for understanding mothers’ vaccination decision-making in low resources settings.

The SARS-CoV-2 virus, which is responsible for the COVID-19 pandemic which emerged and spread, has sparked intense research on its spike protein, which is essential for viral entrance into host cells. Viral reproduction and transmission, host immune response regulation, receptor recognition and host cell entrance mechanisms, as well as structural and functional effects have all been linked to mutations in the spike protein. Spike protein mutations can also result in immune evasion mechanisms that impair vaccine effectiveness and escape, and they are linked to illness severity and clinical consequences. Numerous studies have been conducted to determine the effects of these mutations on the spike protein structure and how it interacts with host factors. These results have important implications for the design and development of medicines and vaccines based on spike proteins as well as for the assessment of those products' efficiency against newly discovered spike protein mutations. The paper gives a general overview of how spike protein mutations are categorized and named, as well as the genomic and phylogenetic techniques that have been used to track their genesis and dissemination. Additionally, it looks at the links between spike protein mutations and clinical outcomes, illness severity, unanswered problems, and future research prospects. Additionally, explored are the effects of these mutations on vaccine effectiveness as well as the possible therapeutic targeting of spike protein mutations.

More than 600 Healthcare workers died due to COVID-19 infection until January 2022 in Ecuador. Even though the COVID-19 vaccines are safe, local, and systemic reactions were reported among physicians. This study aims to analyze the Adverse events (AEs) of COVID-19 vaccines with an emphasis on homologous and heterologous booster doses. An electronic survey was performed in Quito- Ecuador, directed to physicians who were vaccinated with the three doses of COVID-19 vaccines. 210 participants were analyzed after administering any doses of the vaccines. At least one AE was identified in 60.0% (126/210) of the sample after the first dose, 52.40% (110/210) after the second dose, and 75.2% (158/210) after the booster dose. The most frequent AEs were localized pain, myalgia, headache, and fever. At least one drug was used in 44.3% of the population after the first dose, 37.1% after the second dose, and 63.8% in the booster dose. Heterol-ogous booster produces more AEs compared with homologous booster (80.1% vs. 53.8%), and 77.3% of participants reported that interfered with daily activities. Similar studies agree that reactogenicity occurs mainly with heterologous vaccination compared to ho-mologous vaccination. This situation affected physicians’ performance in daily activities and led them to use medication for the symptoms

The global COVID-19 pandemic claiming global spread continues to evolve, now to the verge of a third wave of outbreak possibly caused by the novel variants of concern of severe acute respiratory syndrome corona virus-2 (SARS-CoV-2). The test positivity rate (TPR) and case fatal-ity rate (CFR) have increased steeply in the second wave of COVID-19 compared to the first. From the example of Kerala, a state in southern India, positivity increased from 1.33% at the peak of wave one in 10th June 2020 to 13.45% during 10th June 2021 in the second wave of pandemic. SARS-CoV-2 is an enveloped single-stranded RNA virus. Angiotensin-Converting Enzyme-2 (ACE-2) is a trans membrane surface protein present on multiple types of cells in the human body to which the viral spike protein attaches. Genetic variations in the SARS-CoV-2 and ACE2 receptor can affect the transmission, clinical manifestations, mortality and the efficacy of drugs and vaccines for COVID-19. Mutations are the primary cause of genetic variations. Given the high TPR and CFR, it is necessary to understand the variations of SARS-CoV-2 and cellular receptors of SARS-CoV-2 at the molecular level. In this review, we summarize the impact of genetic and ep-igenetic variations in determining COVID-19 pathogenesis and disease outcome.

The current COVID-19 pandemic is one of the most devastating events in recent history. The virus causes relatively minor damage to young, healthy populations, imposing life-threatening danger to the elderly and people with diseases of chronic inflammation. So, if we could reduce the risk for vulnerable populations, it would make the COVID-19 pandemic more similar to other typical outbreaks. Children do not suffer from COVID-19 as much as their grandparents and have a much higher melatonin level. Bats also do not suffer from the virus they transmit, and bats too have a much higher level of melatonin. Viruses generate an explosion of reactive oxygen species, and melatonin is the best natural antioxidant that is lost with age. Melatonin inhibits the programmed cell death which coronaviruses induce, causing significant lung damage. Coronavirus causes inflammation in the lungs which requires inflammasome activity. Melatonin blocks the inflammasome. The immune response is impaired by anxiety and sleep deprivation. Melatonin improves sleep habits, reduces anxiety and stimulates immunity. Fibrosis may be the most dangerous complication after COVID-19. Melatonin is known to prevent fibrosis. Mechanical ventilation may be necessary but yet imposes risks due to oxidative stress, which can be reduced by melatonin. Thus, by using the safe over-the-counter drug melatonin, we may be immediately able to prevent the development of severe disease symptoms in coronavirus patients, reduce the severity of their symptoms, and/or reduce the negative effects of coronavirus infection on patients’ health after the active phase of the infection is over.

Human papillomavirus (HPV) is associated with cellular changes of the cervix leading to cancer, which highlights the importance of vaccination in preventing HPV infections and subsequent cellular changes. Women undergoing treatment (LEEP) for high-grade cervical intraepithelial neoplasia (CIN2+) remain at risk for recurrence. This study assesses the effect of post-conization HPV vaccination on the viral status of women six months post-conization, aiming to evaluate the vaccine's effectiveness in preventing recurrence of CIN2+. A retrospective cohort study was conducted among women in Troms and Finnmark who underwent conization in 2022. Using the SymPathy database and the national vaccination register (SYSVAK), we analyzed the vaccination status and HPV test results of women born before 1991, who had not received the HPV vaccine prior to conization. Out of 419 women undergoing conization, 243 met the inclusion criteria. A significant association was found between post-conization HPV vaccination and a negative HPV test at six months follow-up (ARR = 12.1%, P = 0.039). Post-conization HPV vaccination significantly reduced the risk of a positive HPV test at the first follow-up, suggesting its potential in preventing recurrence of high-grade cellular changes. The retrospective design and the insufficient control of confounding variables underscore the necessity for further studies to confirm these findings.

The relationship between pangolin-CoV and SARS-CoV-2 has been a subject of debate. Further evidence of a special relationship between the two viruses can be found by the fact that all known COVID-19 viruses have abnormally hard outer shell (low M disorder; i.e., low content of intrinsically disordered residues in the membrane (M) protein) that so far was found in CoVs associated with burrowing animals, such as rabbits and pangolins, in which transmission involves virus remaining in buried feces for a long time. While a hard outer shell is necessary for viral survival, a harder inner shell could also help. For this reason, the N disorder range of pangolin-CoVs, not bat-CoVs, more closely matches that of SARS-CoV-2 especially when Omicron is included. The low N disorder (i.e., low content of intrinsically disordered residues in the nucleocapsid (N) protein), first observed in pangolin-CoV-2017 amd later in Omicron, is associated with attenuation according to the Shell-Disorder-Model. Our experimental study revealed that pangolin-CoV-2017 and SARS-CoV-2 Omicron (XBB.1.16 subvariant) show similar attenuations with respect to viral growth and plaque formation. Subtle differences have been observed that are consistent with disorder-centric computational analysis.

We investigated how Artificial Intelligence (AI) reveals factors shaping COVID-19 vaccine hesitancy among healthcare providers by examining their open-text comments. We conducted a longitudinal survey starting in spring of 2020 with 38,788 current and former female nurses in three national cohorts to assess how the pandemic has affected their livelihood. In January and March-April 2021 surveys, participants were invited to contribute open-text comments and answer specific questions about COVID-19 vaccine uptake. A closed-ended question in the survey identified vaccine-hesitant (VH) participants who either had no intention or were unsure of receiving a COVID-19 vaccine. We collected 1,970 comments from VH participants and trained two Machine Learning (ML) algorithms to identify behavioral factors related to VH. The first predictive model classified each comment into one of three Health Belief Model (HBM) constructs (barriers, severity, and susceptibility) related to adopting disease prevention activities. The second predictive model used the words in January comments to predict the vaccine status of VH in March-April 2021; vaccine status was correctly predicted 89% of the time. Our results showed that 35% of VH participants cited barriers, 17% severity, and 7% susceptibility to receiving a COVID-19 vaccine. Out of the HBM constructs, the VH participants citing a barrier, such as allergic reactions and side effects, had the most associated change in vaccine status from VH to later receiving a vaccine.

The interrelatedness of social-structural aspects and psychological features with the vaccination intention provides the context to explore personal psychological fea-tures related to general decision-making and vaccine-related dispositions, and their contribution to the intention to vaccinate, within post-pandemic circumstances, after the imposed possibility of choosing a vaccine brand. The aim of our study was to map the function (promotive, protective, risk, vulnerability) of a set of psychological aspects in the intention to vaccinate, in people with different social roles regarding the vaccination. We surveyed three samples of people: healthcare providers (HPs), parents, and lay people, within the context of the after-pandemic. Negative vaccine attitudes lower intention to vaccinate in all regression models (all βs ranging from -.128 to -.983, all ps < .01). The main results indicate that, regardless of the sam-ple/social role, there is a shared attitudinal core for positive vaccination intention. This core consists of [high] trust in large corporations, government, and healthcare systems, as well as perceived consensus on vaccine safety/efficacy and experience of freedom (protective factors), and [low] vaccination conspiracy beliefs, trust in social media, and choice overload (risk and vulnerability factors, respectively). There are no common promotive factors of intention to vaccinate; for parents, perceived consensus on vaccines, and trust in corporations and the healthcare system play such roles, for HPs experience of freedom is obtained as a unique promotive factor. In contrast, for laypeople, no unique promotive factors were found. These results and guidelines for the promotion of positive vaccination behavior are further discussed.

Since its emergence, COVID-19 has caused a great impact in health and social terms. Governments and health authorities have attempted to minimize this impact by enforcing different mandates. Recent studies have addressed the relationship between various socioeconomic variables and compliance level to these interventions. However, little attention has been paid to what constitutes people's response and whether people behave differently when faced with different interventions. Data collected from different sources show very significant regional differences across the United States. In this paper, we attempted to shed light on the fact that a response may be different depending on the health system capacity and each individuals’ social status. For that, we analyzed the correlation between different societal variables (i.e. education, income levels, population density, etc.) along with healthcare capacity related variables (i.e. hospital occupancy rates, percentage of essential workers, etc.) with regards to people's level of compliance with three main governmental mandates in the United States: mobility restrictions, mask adoption, and vaccine participation. Our aim was to isolate the most influential variables impacting behavior in response to these policies. We found that there was a strong relationship between individuals' educational levels and political preferences with respect to compliance with each of these mandates.

A major advance of drug discovery and targeted therapy directed to cancer cells may be achieved by exploitation and immunomodulation of their unique biological property. This re-view summarizes our efforts to develop novel chemo-thermo-immuno-therapy (CTI therapy) by conjugating a melanogenesis substrate, N-propionyl cysteaminylphenol (NPrCAP: amine analog of tyrosine), with magnetite nanoparticles (MNP). In our approach, NPrCAP provides a unique drug delivery system (DDS) because of its selective incorporation into melanoma cells. It also functions as a melanoma-targeted therapeutic drug because of its production of highly reactive free radicals (melanoma-targeted chemotherapy). Moreover, utilization of MNP is a platform to develop thermo-immunotherapy because of heat shock protein (HSP) generation upon exposure to an alternating magnetic field (AMF). The feasibility of our approach was successfully shown in experimental in vivo and in vitro mouse melanoma models and in preliminary clinical trials to a limited number of advanced melanoma patients.

Foot-and-mouth disease virus (FMDV) causes the highly contagious foot-and-mouth disease, which is characterized by the appearance of vesicles in and around the mouth and feet of cloven-hoofed animals. BHK21 cells are the cell line of choice for the propagation of FMDV for vaccine production world-wide but vary in their susceptibility for different FMDV strains. Previous studies showed that the FMDV resistance of a certain BHK cell line can be overcome by using a closely related but permissive cell line for the pre-adaptation of the virus, but the adapted strains were found to harbor several capsid mutations. In this study, these adaptive mutations were introduced into the original Asia-1 Shamir isolate individually or in combination to create a panel of 17 Asia-1 mutants by reverse genetics and examine the effects of the mutations on receptor usage, viral growth, immunogenicity and stability. A single amino acid exchange from glutamic acid to lysine at position 202 in VP1 turned out to be of major importance for productive infection of the suspension cell line BHK-2P. In consequence, two traditionally passage-derived strains and two recombinant viruses with a minimum set of mutations were tested in vivo. While the passaged-derived viruses showed a reduced particle stability, the genetically modified viruses were more stable but did not confer a protective immune response against the original virus isolate.

The resurgence of mpox, particularly in regions where the virus was previously non-endemic, has reignited interest in the cross-protective potential of smallpox antibodies. Given the genetic similarity between the mpox virus and variola virus (the causative agent of smallpox), antibodies generated against smallpox may offer a degree of protection against mpox. This study investigates the presence of smallpox and mpox antibodies in human immunoglobulin preparations containing IgG against both mpox virus and vaccinia virus using ELISA techniques. The implications of these findings for post-exposure prophylaxis (PEP) are discussed in light of the recent mpox outbreaks in Africa, as reported by the World Health Organization (WHO). Current data suggest that smallpox vaccination, even decades after eradication, may confer substantial protection against mpox, thereby serving as a critical tool in managing emerging outbreaks. Further the presence of mpox antibodies in immunoglobulin preparations was also significant. These findings strongly suggest the potential use of intravenous immunoglobulins preparation as possible therapeutic strategy. Particularly it also underscores the need for further research into the development of targeted post-exposure prophylaxis strategies that leverage the cross-reactivity of orthopoxvirus antibodies.

The main proteinase (Mpro), or 3CLpro, is a critical enzyme in the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) lifecycle and is responsible for breaking down and releasing vital functional viral proteins crucial for virus development and transmission. As a catalytically active dimer, its dimerization interface has become an attractive target for antiviral drug development. Recent research has extensively investigated the enzymatic activity of Mpro, focusing on its role in regulating the coronavirus replication complex and its significance in virus maturation and infectivity. Computational investigations have identified four druggable pockets, suggesting potential allosteric sites beyond the substrate-binding region. Empirical validation through site-directed alanine mutagenesis targeted residues in both the active and allosteric regions corroborated these predictions. Structural studies of drug target proteins can inform therapeutic approaches, with metadynamics simulations shedding light on the role of H163 in regulating Mpro function and providing insights into its dynamic equilibrium to the wild-type enzyme. Despite the efficacy of vaccines and drugs in mitigating SARS-CoV-2 spread, ongoing viral evolution, selective pressures, and continued transmission pose challenges, potentially leading to resistance mutations. Phylogenetic analyses indicated the existence of several resistance variations predating drug introduction to the human population, emphasizing the likelihood of drug spread. Hydrogen/deuterium-exchange mass spectrometry reveals the structural influence of the mutation, while clinical trials on 3CLPro inhibitors underscore the clinical significance of reduced enzymatic activity and offer avenues for future therapeutic exploration. Understanding the implications of 3CLPro mutations holds promise for shaping forthcoming therapeutic strategies against COVID-19. This review delves into factors influencing mutation rates and identifies areas warranting further investigation, providing a comprehensive overview of Mpro mutations, their categorization, and terminology. Moreover, we examined their associations with clinical outcomes, illness severity, unresolved issues, and future research prospects, including their impact on vaccine efficacy and potential therapeutic targeting.

SARS-CoV-2 virulence is known to increase with lowering of environmental temperature and solar ultraviolet radiation; therefore, we have focused our real-world nationwide study concerning with COVID-19 trends and dynamics on the coldest seasons of the year in Italy, the Western country hardest hit at the onset of the pandemic, comparing the autumn-winter of 2020 (before mass vaccination but when the emergency machinery was fully operative in terms of tracing and swabs) with the autumn-winter of 2021 (after mass vaccination), and analyzing the mortality burden by age groups and life stages in the years 2019 (pre-COVID-19), 2020 (before mass vaccination) and 2021 (after mass vaccination). Methods: During the state of national health emergency, the Civil Defense Department released the aggregate data coming from the Higher Institute of Health, the Ministry of Health, the Italian Regions, and the Independent Provinces, to inform the population (58.85 million people) about the pandemic situation, daily. Among these data there were the number of contagions, performed swabs, hospitalizations in Intensive Care Units (ICU), non-ICU patients, and deaths. By means of a team effort, we have collected and elaborated all these data, comparing the COVID-19 pandemic in Italy during the autumn-winter of 2020 with the autumn-winter of 2021. Moreover, we have extracted from the database of the National Institute of Statistics the total number of annual deaths in Italy during the years 2019, 2020 and 2021, comparing them to each other in order to evaluate the mortality burden attributable to COVID-19. Results: From the autumn-winter of 2020 to the autumn-winter of 2021, the contagions increased by ≈285%, however against a ≈290% increase in the performed swabs; therefore, the mean positivity rate passed from 8.74% before mass vaccination to 8.59% after mass vaccination. The unprecedent vaccination campaign allowed a ≈251% abatement in COVID-19 deaths, and a reduction of ≈224% and ≈228% in daily ICU and non-ICU hospitalizations due to COVID-19, respectively. Regarding COVID-19 deaths, in 2020 there was a mortality excess of ≈14.3% quantifiable in 105,900 more deaths compared to 2019, the pre-COVID-19 year; 103,183 out of 105,900 deaths occurred in older adults (≥60 years), which is equivalent to ≈97.4%, while in adults over 50, the segment of population just below older adults, in 2020 there were 2807 more deaths than in 2019. Surprisingly, from the analysis of our data, it is emerged that under the age of 40 in the years 2019, 2020 and 2021 there were 7103, 6808 and 7165 deaths, respectively. This means that in subjects under 40 during 2020 there were 295 fewer deaths than in 2019, while during 2021 there were 357 more deaths than in 2020, equivalent to ≈5.2% more. Conclusions: COVID-19 is a potential life-threatening disease mainly in older adults, as they are the most vulnerable due to inherent immunosenescence and inflammaging. Extensive vaccination in this segment of population with up-to-date vaccines is the means to reduce deaths, hospitalizations, and ICU pressure in the public interest. In the event of future threats, a new mass vaccination campaign must not be implemented without taking into account the individual age; it should primarily be aimed at people over 60 and at patients of any age with immune deficits, and secondly at people over 50. COVID-19 vaccination shows a favorable benefit-risk balance in older adults, while this balance falls under the age of 40; this younger segment of population should be therefore exempt from any mandatory vaccination.

Nano-drugs and nano-delivery systems are rapidly evolving, with new strategies emerging in the current practices. The evolution of these technologies began with modifying the chemical structure, progressing to supramolecular ionic complexes, and culminating in elegant ad hoc delivery systems. Nanoparticles have numerous benefits as a carrier system for delivering therapeutic agents to intra-arterial sites. These benefits include their subcellular size, targeted surfaces, good suspensibility, and uniform dispersity, making them an ideal choice for catheter-based delivery. Despite the advancements made in the field of nano-drugs and nano-delivery systems, there are still some hurdles to overcome in terms of their commercial availability.The current review presents an updated summary of recent advancements in nano-drugs and nano-delivery systems, including their commercial availability. We aim to discuss the present challenges and prospects of commercially available nano-drugs and nano-delivery systems. Here, we provide a precise and informative overview of the current state of these technologies and underscore the potential they hold for future developments. Further, we have categorized commercially available modifications, name, parent company and their main applications in nano-drugs.

Breakthrough COVID-19 (occurring in fully vaccinated people) has been described. Data on its characteristics among immune mediated rheumatic disesases (IMRD) patients are scarce. This study describes breakthrough COVID-19 among IMRD patients participating of SAFER-study, a Brazilian multicentric cohort evaluating safety, effectiveness and immunogenicity of SARS-Cov-2 vaccines in autoimmune diseases. Descriptive analysis and a binary logistic regression model, to evaluate predictors of COVID-19-related hospitalization, were performed. P-value < 0.05 was significant. The included 160 patients were predominantly females (83.1%), with mean (SD) age 40.23 (13.19) years. Patients received 2 (19%), 3 (70%) or 4 (11%) vaccine doses. The initial two-dose series was mainly with ChAdOx1 (Oxford/AstraZeneca) (58%) or BBIBP-CorV (Sinopharm-Beijing) (34%). The first booster (n=150) was with BNT162b2 (BioNtech/Fosun Pharma/Pfizer) (63%) or ChAdOx1 (29%). The second booster (n=112) was with BNT162b2 (40%) or ChAdOx1 (26%). COVID-19 hospitalization rate was 17.5%. IMRD moderate/high activity (OR: 5.84, CI: 1.9-18.5, p=0.002) and treatment with corticosteroids (OR: 2.94, CI: 1.02-8.49, p=0.0043) associated with higher odds of hospitalization, while the increasing number of vaccine doses was protective (OR: 0.37, CI: 0.15-0.9, p=0.032). These findings, along with previous reassuring results about the safety of the COVID-19 vaccines, argue in favour of booster vaccination in IMRD patients.

Background: The COVID-19 pandemic has exacerbated existing healthcare disparities among American Indian/Alaska Native (AI/AN) populations, rooted in historical traumas and systemic marginalization. Methods: This study conducted at a single Indian Health Service (IHS) clinic in central Michigan examines the effectiveness of educational interventions in enhancing COVID-19 knowledge and attitudes among AI/AN populations. Utilizing a pre/post prospective study design, participants received either a video or infographic educational intervention, followed by a survey assessing COVID-19 knowledge and attitudes. Results: The results indicate significant improvements in knowledge and attitudes post-intervention, with both modalities proving effective. However, specific factors such as gender, political affiliation, and place of residence influenced COVID-19 attitudes and knowledge, emphasizing the importance of tailored interventions. Conclusions: Despite limitations, this study highlights the critical role of educational interventions in addressing vaccine hesitancy and promoting health equity within AI/AN communities. Moving forward, comprehensive strategies involving increased Indian Health Service funding, culturally relevant interventions, and policy advocacy are crucial in mitigating healthcare disparities and promoting health equity within AI/AN communities.

Vaccine-induced immune thrombotic thrombocytopenia (VITT) is a rare but severe adverse event that was first observed during the global vaccination campaign against SARS-CoV-2 infection, specifically in those receiving adenoviral vector-based vaccines for Coronavirus disease 2019 (COVID-19). VITT develops 4 to 42 days post-vaccination and is characterized by the development of platelet-activating anti-platelet factor 4 (PF4) antibodies, leading to thrombocytopenia and thrombosis at unusual sites. The rise in awareness and subsequent prompt recognition of VITT was paramount in reducing mortality. Moreover, as vaccination campaigns around the world continue, a better understanding of VITT not only has important clinical implications but is also crucial for future vaccine development. In this review, we summarize the clinical features, pathophysiology, and incidence rates of VITT as well as highlight other anti-PF4 antibody-mediated disorders of growing clinical significance.

We conducted a monocentric observational study aimed at evaluating the pharmaceutical service provided at a Community Pharmacy (C.PH.) during pandemia in our Puglia Region in the period from 29.12.2021 to 12.03.2022 on 550 patients of various ages, sexes, and with concomitant diseases. We collected anamnestic data and any post-vaccination adverse reactions. Interviews with the integrated EQ5 method on evaluating the quality of the service offered and any therapy preference were also performed. As expected, the vaccines were reactogenic after the first dose in the patients with mild-moderate reactions with younger age and female gender as risk factors. Immune-allergic reactions of moderate-severe degree were observed in adult females. In the elderly, the vaccination procedure was well tolerated. Comirnaty showed a favorable O.R.<;1 vs other vaccines. No myocarditis and thromboembolic events in our population were observed. All treatments in May 2023 were correlated with a viremia trend, Paxlovid was prescribed in 3% of the patients in our center and in 1.46% in the Puglia Region with no effects in the hospitalization. It was distributed/dispensed by a novel on behalf of third parties distribution/dispensation (D.P.C.) protocol by the C.PH. The C.PH. resulted in a safe vaccination center providing appropriate patient inclusion during vaccination.

People must have particular personality traits and social resources, also known as health literacy, in order to access, comprehend, and use information to make decisions about their health. Patients' ability to engage in complex disease management and self-care is strongly related to their level of health literacy. It can help us stay healthy by preventing illness and effectively managing existing illnesses. People with low health literacy (LHL) may find it difficult to manage their condition and prevent illness, which may lead to increased use of healthcare services. Furthermore, LHL is associated with increased hospitalizations, increased use of emergency care, decreased use of preventative services, and a worsened ability to understand labels and health messages, a worsened state of health, higher mortality, and more expensive medical care.

Several vaccines against COVID -19 have been developed and licenced to enhance the immune response against SARS-CoV-2. Similarly, infection with SARS-CoV-2 before vaccination has been shown to provide significant protection against severe infection and hospitalisation. The aim of this study was to investigate the effect of three doses of Sinopharm vaccine and SARS-CoV-2 infection on the specific immune response in 103 volunteers, measuring neutralizing antibodies, anti-S1 IgG, anti-RBD IgM, anti-N IgM, anti-N IgG antibodies and interferon γ. Our results showed that the presence of cardiovascular diseases increased the level of anti-N-IgG antibodies, while endocrinological diseases decreased the level of neutralizing antibodies and anti-N-IgG antibodies, suggesting that these diseases alter the effect of vaccine immunity. In addition, there was a significant decrease in anti-S1 IgG levels 6 months and in anti-N IgG levels 18 months post-infection, while neutralizing antibody and interferon γ levels were constant at 3, 6 and 18 months post-infection. Therefore, our results confirm the importance of hybrid immunity as the strongest and most durable compared to exclusively natural or vaccine-induced immunity. Significant positive correlations were found between humoral and cellular immunity markers: neutralizing antibodies, anti-S1 IgG, anti-N IgG and interferon γ, indicating a unique coordinated response specific to COVID-19.

A model to predict the relative levels of respiratory and fecal-oral transmission potentials of coronaviruses (CoVs) by measuring the percentage of protein intrinsic disorder (PID) of the M (Membrane) and N (nucleoprotein) proteins in their outer and inner shells, respectively, was built before the MERS-CoV outbreak. Application of this model to the 2003 SARS-CoV indicated that this virus with M_PID = 8.6% and N_PID = 50.2% falls into group B, which consists of CoVs with intermediate levels of both fecal-oral and respiratory transmission potentials. Further validation of the model came with MERS-CoV (M_PID = 9%, N_PID = 44%) and SARS-CoV-2 (M_PID = 5.5%, N_PID = 48%) falling into the groups C and B, respectively. Group C contains CoVs with higher fecal-oral but lower respiratory transmission potentials. Unlike SARS-CoV, SARS-CoV-2 with M_PID = 5.5% has one of the hardest outer shells among CoVs. This shell hardness is believed to be responsible for high viral loads in the mucus and saliva making it more contagious than SARS-CoV. The hard shell is able to resist the anti-microbial enzymes in body fluids. Further searches have found that high rigidity of outer shell is characteristic for the CoVs of burrowing animals, such as rabbits (M_PID = 5.6%) and pangolins (M_PID = 5-6%), which are in contact with the buried feces. A closer inspection of pangolin-CoVs from 2017-19 reveals that these animals provided a unique window of opportunity for the entry of an attenuated SARS-CoV-2 precursor into the human population in 2017 or earlier, with the subsequent slow and silent spread as a mild cold that followed by its mutations into the current more virulent form. Evidence of this lies in the similarity of shell disorder and genetic proximity of the pangolin-CoVs to SARS-CoV-2 (~90%). A 2017 pangolin-CoV strain shows evidence of higher levels of attenuation and higher fecal-oral transmission associated with lower human infectivity via having lower N_PID (44.8%). Our shell disorder analysis also revealed that lower inner shell disorder is associated with the lesser virulence in a variety of viruses.

A model that predicts levels of coronavirus (CoV) respiratory/fecal-oral transmission potentials based on the outer shell hardness has been built using neural network (artificial intelligence, AI) analysis of the percentage of disorder (PID) in the nucleocapsid, N, and membrane, M, proteins of the inner and outer viral shells, respectively. Based mainly on the PID of N, SARS-CoV-2 is categorized as having intermediate levels of both respiratory and fecal oral transmission potential. Related to this, other studies have found strong positive correlations between virulence and inner shell disorder among numerous viruses, including Nipah, Ebola, and Dengue viruses. There is some evidence that this is also true for SARS-CoV-2 and SARS-CoV, which have N PIDs of 48% and 50%, and are characterized by case-fatality rates of 7.1% and 10.9%, respectively. The link between levels of respiratory transmission and virulence lies in viral load of body fluids and organ respectively. A virus can be infectious via respiratory modes only if the viral loads in saliva and mucus exceed certain minima. Likewise, a person may die, if the viral load is too high especially in viral organs. Inner shell proteins of viruses play important roles in the replication of viruses, and structural disorder enhances these roles by providing greater efficiency in protein-protein/DNA/RNA/lipid binding. This paper outlines a novel strategy in attenuating viruses involving comparison of disorder patterns of inner shells of related viruses to identify residues and regions that could be ideal for mutation. The M protein of SARS-CoV-2 has one of the lowest M PID values (6%) in its family, and therefore this virus has one of the hardest outer shells, which makes it resistant to antimicrobial enzymes in body fluid. While this is likely responsible for its contagiousness, the risks of creating an attenuated virus with a more disordered M are discussed.

Currently available seasonal influenza vaccines confer variable protection due to antigenic changes resulting from accumulation of diverse mutations. Analysis of new seasonal influenza vaccines is challenging in part due to limitations of the traditional hemagglutination inhibition (HAI) assay with A/H3N2 strains. An improved and objective novel HAI assay was developed using recombinant virus-like particles (VLPs) and egg-derived virus as agglutinins, oseltamivir treatment of VLPs, human red blood cells, and using an automated image reader-based analysis of hemagglutination. HAI validation was demonstrated using four VLP and egg-derived strains, with 46–56 serum samples tested 12 times in duplicate per strain. The validated HAI assay was precise as indicated by the percent geometric coefficient of variation for intra-, inter-, and total-assay precision, and accurate as evidenced by % bias measurements. The assay exhibited linearity, specificity for homologous type/subtype strains, and sensitivity with a starting dilution of 1:10. Assay robustness and sample stability were demonstrated as a % difference compared to reference condition. Validated HAI results were equivalent for singleton and duplicate sample testing and correlated well with a qualified live wild-type influenza microneutralization assay. These findings demonstrate the suitability of this high-throughput novel modified validated HAI assay, for evaluating vaccine immunogenicity and efficacy.

We tested the possibility of using “adverse events count” (AEC) as a drug-risk indicator and side-effect severity indicator. Data from 3938 adverse event (AE) reports for COVID-19 vaccines (Comirnaty, Moderna, Vaxzevria, and Janssen) and 6869 AE reports for other medicines were collected from the Bulgarian Drug Agency database (01.01.2018–31.03.2022). AEC was modeled with zero-adjusted negative binomial (ZANBI) and zero-adjusted Poisson inverse Gaussian (ZAPIG) regression models, which account for zero absence and overdispersion. The models’ fit was checked with residual diagnostic plots and parametric correspondence to normality. Explanatory variables were: age, sex, sequence number (order of submission), severity of AE, and vaccine type. Average AEC was higher in severe vs. non-severe AE, and in females vs. males; it decreased with age and was lower in Comirnaty than other vaccines. Variability of AEC for COVID-19 data decreased with sequence number in severe AE and increased in non-severe AE. Full ZANBI models had greater sensitivity than parametric ZANBI or ZAPIG models. Results showed correlation between AEC and AE severity, suggesting AEC as a simple and reliable measure of drug-risk and side-effect severity for clinicians and regulators, especially for COVID-19 vaccines.

This proposal was prepared in the very first weeks of 2020 because of the outbreak of COVID-19.There is good reason to suppose that rotavirus vaccine can be used as protection tool to effectively and safely fight and mitigate SARS-CoV-2 infection and the impact caused by COVID-19 in adult humans, due to the development of cross and trained immunity following rotavirus vaccination. Up-to-date, some rotavirus vaccines are available and approved, two of them have a large experience in results and safety. Little experience has been achieved in the use of rotavirus vaccine in adults. However, it can be expected that it would be safe and effective in adults and in the elderly as well. This proposal explains the background.

-529391451442Citation: To be added by editorial staff during production. Academic Editor: Firstname Lastname Received: date Revised: date Accepted: date Published: date Copyright: © 2023 by the authors. Submitted for possible open access publication under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).0Citation: To be added by editorial staff during production. Academic Editor: Firstname Lastname Received: date Revised: date Accepted: date Published: date Copyright: © 2023 by the authors. Submitted for possible open access publication under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).Abstract: SARS-CoV-2 vaccination offered the opportunity to get out of the pandemic and thereby worldwide health, social, and economic disasters. However, in addition to efficacy, safety is an important issue for any vaccine. The mRNA-based vaccine platform is considered to be safe but side effects are being reported more frequently as more and more people around the world become treated. Myo-pericarditis is the major, but not the only cardiovascular complication of this vaccine, hence it is important not to underestimate other side effects. We report a case series of patients affected by cardiac arrhythmias post mRNA vaccine from our clinical practice and the literature. Reviewing the official vigilance database emerged that heart rhythm disorders after Covid vaccination are not uncommon and deserve more clinical and scientific attention. Since Covid vaccine is the only vaccination to have been related to this side effect questions arose about whether these vaccines could affect heart conduction. Although the risk-benefit is clearly in favor of vaccination heart rhythm disorders are not a negligible issue and there are red flags in the literature about the risk of post-vaccination malignant arrhythmias in some predisposed patients. In light of these findings, we investigated the potential mechanism for the Covid vaccine to impact on cardiac electrophysiology and cause heart rhythm disorders.

Severe acute respiratory syndrome coronavirus 2 (SARS-Cov-2/2019-nCoV) infection is an emerging pandemic. The virus binds to angiotensin converting enzyme 2 (ACE2) and TMPRSS2 which are abundantly expressed on various human cells including lung epithelial cells and intestinal cells and the virus can infect these cells. Currently no specific treatments or vaccines are available for this disease. A per oral live attenuated vaccine can be beneficial in SARS-Cov-2 infection because the attenuated virus initially infects the gut, stimulates the mucosa associated immune system sparing the respiratory system during the initial immune response. The live virus can also spread in the community boosting herd immunity.

Maternal-derived immunity is a critical component for survival and success of offspring in pigs to protect from circulating pathogens like Type 2 Porcine Reproductive and Respiratory Syndrome Virus (PRRSV-2). The purpose of this study was to investigate the transfer of anti-PRRSV immunity to piglets from gilts that received modified-live virus (MLV) alone (TRT 0), or in combination with one of two autogenous inactivated vaccines (AIVs, TRT 1+2). Piglets from these gilts were challenged with the autogenous PRRSV-2 strain at two weeks of age and their adaptive immune response (IR) was evaluated until 4 weeks post inoculation (wpi). The systemic humoral and cellular IR was analyzed in the pre-farrow gilts, and in piglets, pre-inoculation, and at 2- and 4-wpi. Both AIVs partially protected the piglets with reduced lung pathology and increased weight gain; TRT 1 also lowered piglet viremia best explained by the AIV-induced production of neutralizing antibodies in gilts and their transfer to the piglets. In piglets, pre-inoculation, the main systemic IFN-γ producers were CD21α+ B cells. From 0 to 4 wpi, the role of these B cells declined and CD4 T cells became the primary systemic IFN-γ producers. In lungs, CD8 T cells were the primary and CD4 T cells the secondary IFN-γ producers including a novel subset of porcine CD8α-CCR7- CD4 T cells, potentially terminally differentiated CD4 TEMRA cells. In summary, this study demonstrates that maternal AIV vaccination can improve protection of pre-weaning piglets against PRRSV-2; it shows the importance of transferring neutralizing antibodies to piglets; and it introduces two novel immune cell subsets in pigs – IFN-γ producing CD21α+ B cells and CD8α-CCR7- CD4 T cells.

O26 enteropathogenic Escherichia coli (EPEC), possesses a unique pseudocapsule composed of polysaccharides identical to the O antigen in their lipopolysaccharide (LPS) membrane. Therefore, the impact of O26 polysaccharides on the immune evasion mechanisms of capsulated O26 EPEC was investigated. Our findings reveal that the concentration of GlcNAc, an immunodominant unit of O26 polysaccharides capable of activating the MBL (Mannose Biding Lecting) pathway of the complement system, was found to be lower in capsulated EPEC O26 compared to naked shiga toxin-producing E. coli (STEC) O26 strain. It was noted that, unlike the naked STEC strain, the capsulated EPEC O26 strain was protected against lysis by the alternative pathway of the com-plement system by inhibiting C3b adhesion to its bacterial surface. Capsulated EPEC O26 strains were also able to avoid phagocytosis by macrophages. However, the immune evasion provided by the capsule was overcome in the presence of anti-O26 polysaccharide antibodies. Additionally, these antibodies were able to recognize O26 EPEC in the presence of biofilm and inhibit their adhesion to human epithelial cells. Overall, the results indicate that the O26 polysaccharides can generate an effective humoral immune response, making them promising antigens for the de-velopment of a vaccine against capsulated O26 E. coli

The human antibody response to influenza virus infection or vaccination is as complicated as it is essential for protection against flu. The constant antigenic changes of the virus to escape human herd immunity hinder the yearly selection of vaccine strains since it is hard to predict which virus strains will circulate for the coming flu season. A "universal" influenza vaccine that could induce broad cross-influenza subtype protection would help to alleviate this burden. However, the human antibody response is intricate and often obscure, with factors like antigenic seniority or original antigenic sin "OAS", and back-boosting ensuring that each person mounts a unique immune response to infection or vaccination with any new influenza virus strain. Notably, the effects of existing antibodies on cross-protective immunity after repeated vaccinations are unclear. More research is needed to characterize the mechanisms at play, but traditional assays such as hemagglutinin inhibition (HAI) and microneutralization (MN) are excessively limited in scope and too resource-intensive to effectively meet this challenge. In the past ten years, new multiple dimensional assays (MDAs) have been developed to help overcome these problems by simultaneously measuring antibodies against a large panel of influenza hemagglutinin (HA) proteins with a minimal amount of sample in a high throughput way. MDAs will likely be a powerful tool for accelerating the study of the humoral immune response to influenza vaccination and the development of a universal influenza vaccine.

Pediatric onset multiple sclerosis (POMS), characterized by the onset of multiple sclerosis before the age of 18, is gaining increased recognition. Approximately 5 percent of MS cases manifest before the age of 18, with less than 1 percent occurring before the age of 10. Despite its rarity, pediatric MS exhibits distinct characteristics, with an association between younger age at onset and a comparatively slower disease progression. Despite this slower progression, individuals with POMS historically reach disability milestones at earlier ages than those with adult-onset multiple sclerosis. While various immunomodulatory agents demonstrate significant benefits in MS treatment, such as reduced relapse rates and slower accumulation of brain lesions on magnetic resonance imaging (MRI), the majority of disease-modifying therapies (DMTs) commonly used in adult MS lack evaluation through pediatric clinical trials. Current evidence is predominantly derived from observational studies. This comprehensive review aims to consolidate existing knowledge on the mechanisms of action, efficacy, safety profiles, and recommended dosages of available DMTs specifically in the context of pediatric MS. Furthermore, the review outlines recent advancements and explores potential medications still in developmental stages, providing a thorough overview of the current landscape and future prospects for treating POMS.

Chronic HCV infection and associated liver cancer impose a heavy burden on the healthcare system. Direct acting antivirals eliminate HCV, unless it is drug resistant, and partially reverse liver disease, but they cannot cure HCV-related cancer. Possible remedy could be a multi-component immunotherapeutic vaccine targeting both HCV-infected and malignant cells, also those not infected with HCV. To meet this need we developed a two-component DNA vaccine based on the highly conserved core protein of HCV to target HCV-infected cells, and a renowned tumor associated antigen telomerase reverse transcriptase (TERT) based on the rat TERT, to target malignant cells. Their synthetic genes were expression-optimized, and HCV core was truncated after aa 152 (Core152opt) to delete the domain interfering with immunogenicity. Core152opt and TERT DNA were highly immunogenic in BALB/c mice, inducing IFN-γ/IL-2/TNF-α response of CD4+ and CD8+ T cells. Also, DNA-immunization with TERT enhanced cellular immune response against luciferase encoded by a co-delivered plasmid (Luc DNA). However, DNA-immunization with Core152opt and TERT mix resulted in abrogation of immune response against both components. A loss of bioluminescent signal after co-delivery of TERT and Luc DNA into mice indicated that TERT affects the in vivo expression of luciferase directed by the immediate early cytomegalovirus and interferon-β promoters. Panel of mutant TERT variants was created and tested for their expression effects. TERT with deleted N-terminal nucleoli localization signal and mutations abrogating telomerase activity still suppressed the IFN-β driven Luc expression, while the inactivated reverse transcriptase domain of TERT and its analogue, enzymatically active HIV-1 reverse transcriptase, exerted only weak suppressive effects, implying that suppression relied on the presence of the full-length/nearly full-length TERT, but not its enzymatic activity. The effect(s) could be due to interference of the ectopically expressed xenogeneic rat TERT with biogenesis of mRNA, ribosomes and protein translation in murine cells, affecting the expression of immunogens. HCV core can aggravate this effect, leading to early apoptosis of co-expressing cells, preventing the induction of immune response.

Aquaculture is rapidly becoming one of the pivotal sectors in the farm economy, driven by the increasing demand for high-quality animal protein at an affordable cost, especially with the escalating human population. However, the expansion of high-density fish populations also brings forth a challenge – the rapid transmission and spread of infectious disease agents among them. To combat this, vaccination is emerging as a reliable and standardized method for providing immunity against viral and bacterial outbreaks. The ideal vaccine is expected to be safe, effective, economical, and easily administered. The fish vaccination industry continually publishes new information on fish immunology and vaccinology, contributing to the improvement of vaccine formulation and efficacy. This review aims to offer insights into the current status of bacterial, viral, and parasitic diseases, discuss existing vaccinations, and address potential industry-threatening diseases like infectious edwardsiellosis, motile aeromonas septicemia, TiLV, salmon anemia, vibriosis, and white spot disease. Technological advancements have played a crucial role in enhancing our understanding of fish immunological mechanisms, leading to improved vaccine administration and the development of recombinant live attenuated, subunit, DNA, and RNA vaccines. However, challenges such as oral tolerance, vaccine degradation, and stressful environments persist, impacting vaccine efficacy. Addressing these challenges and gaining a deeper understanding of the fish immune system and host-pathogen interactions will be pivotal for future improvements, contributing to the sustainability of aquaculture and enhancing global food security.

COVID-19 sepsis immune response remains unclear. Here we propose a new perspective in host response against pathogenic proteins that may lead to a vaccine design by polymerization of antigens of <70 kDa. In COVID-19, initial Th1 response kills infected cells releasing viral proteins. SARS-CoV-2 viral structural proteins are Spike (140 kDa), Nucleocapsid (50 kDa), Membrane (25 kDa) and Envelope (10 kDa). B cell receptor cannot capture antigens >70 kDa. The Spike protein (140 kDa) cannot be captured by B cells and triggers inflammatory Th1 response via the macrophages. Only proteins with a size <70 kDa can activate B cell receptor and trigger Th2 adaptative humoral response. Moreover, M-25 kDa and E-12 kDa glycoproteins can activate IgM-BCR like oligovalent or monovalent antigens. The sustained infected cells lysis overfeeds high levels of viral proteins <70 kDa, increases B cells activation and, in the shift from Th1 to Th2 immune response, triggers the cytokine storm. The continuous BCR activation increases IL-10 releasing and may lead to immune paralysis.

Each injection of any known vaccine results in a strong expression of pro-inflammatory cytokines. This is the result of the innate immune system activation, without which no adaptive response to the injection of vaccines is possible. COVID-19 mRNA vaccines would not escape this rule. Unfortunately, the degree of inflammation produced by these vaccines is variable, probably depending on the genetic background and previous immune experiences, which through epigenetic modifications, could have made the innate immune system of each individual tolerant or reactive to subsequent immune stimulations.We hypothesize that we can move from a limited pro-inflammatory condition to conditions of increasing expression of pro-inflammatory cytokines that can culminate in multisystem hyperinflammatory syndromes following COVID-19 mRNA vaccines (MIS-V). We have graphically represented this idea in a hypothetical inflammatory pyramid (IP) and we have correlated the time factor to the degree of inflammation produced after the injection of vaccines. Furthermore, we have placed the clinical manifestations within this hypothetical IP, correlating them to the degree of inflammation produced. Surprisingly, excluding the possible presence of an early MIS-V, the time factor and the complexity of clinical manifestations are correlated to the increasing degree of inflammation: symptoms, heart disease and syndromes (MIS-V).

The article titled "Immunoglobulins and Its Applications" provides a comprehensive overview of the structure, function, and therapeutic significance of immunoglobulins, also known as antibodies. These vital proteins, produced by plasma cells in response to immunogens, are essential components of the immune system, playing a critical role in recognizing and neutralizing pathogens such as bacteria and viruses. The article elaborates on the five primary classes of immunoglobulins (IgA, IgD, IgE, IgG, and IgM), each distinguished by its unique structural and functional properties. It discusses the molecular composition of immunoglobulins, highlighting the significance of their variable and constant regions in antigen binding. The paper also explores the diverse immune functions mediated by these proteins, including precipitation, agglutination, and neutralization of antigens. Additionally, the article emphasizes the therapeutic applications of immunoglobulins, particularly in treating immune deficiencies and other diseases. Advances in monoclonal antibody technology have significantly expanded the utility of immunoglobulins in both research and medicine, leading to the development of innovative therapeutic approaches such as humanized monoclonal antibodies and bifunctional antibodies. This comprehensive analysis underscores the critical role of immunoglobulins in both natural immunity and therapeutic interventions.