Background/Objectives: Community-acquired methicillin-resistant Staphylococcus aureus (CA-MRSA) greatly complicates treatment of skin and soft tissue infections (SSTI). It was previ-ously found that subcutaneous (SQ) treatment with the mononuclear phagocyte (MP)-selective activator, complement peptide-derived immunostimulant-02 (CPDI-02; formerly EP67), increases prophylaxis of outbred CD-1 mice against SQ infection with CA-MRSA. Here, we determined if treatment with CPDI-02 also increases curative protection. Methods: Female CD-1 mice were challenged SQ with CA-MRSA USA300 LAC then CPDI-02 or inactive scCPDI-02 was administered by a topical, SQ, IM, or IV route at 6- or 24-hrs post-challenge. Dermal abscess sizes were compared over 10 days and CA-MRSA burden, neutrophils, MP, and pro-inflammatory cytokines were compared in dermal abscesses. CPDI-02 PK and distribution in female CD-1 mice were compared after IM or IV dosing and CPDI-02 toxicity was determined by IM dose escalation and repeat IM dosing in male and female CD-1 mice. Results: Repeat IM treatment with CPDI-02 starting at 6-hrs post-challenge decreased maximum abscess surface area, CA-MRSA burden, and time to resolu-tion, whereas repeat treatment by the topical, SQ, or IV route had no effect. Starting CPDI-02 treatment at 24-hrs post-challenge was ineffective regardless of route. Single IM treatment with CPDI-02 starting at 6-hrs post-challenge was as effective as repeat IM treatment, increased systemic exposure, and decreased initial levels of IL-1β and increased MP in dermal abscesses. CPDI-02 was tolerated to between 130-170 mg/kg for single IM dosing and 65-130 mg/kg for repeat IM dosing with males being more tolerant. Conclusions: Single early-stage IM treatment with CPDI-02 may increase curative protection against SSTI caused by CA-MRSA or other pathogens controlled by activated MP.

Efforts towards an effective HIV-1 vaccine have remained mainly unsuccessful. There is increasing evidence for a potential role of HLA-C-restricted CD8+ T cell responses in HIV-1 control, including our recent report of HLA-C*03:02 among African children. However, there are no documented optimal HIV-1 CD8+ T cell epitopes restricted by HLA-C*03:02; additionally, the structural influence of HLA-C*03:02 on epitope binding is undetermined. Immunoinformatics approaches provide a fast and inexpensive method to discover HLA-restricted epitopes. Here, we employed immunopeptidomics to identify HLA-C*03:02-restricted CD8+ T cell epitopes. We identified a clade-specific Gag-derived GY9 (GTEELRSLY) HIV-1 p17 matrix epitope exclusively restricted to HLA-C*03:02. Residues E62, T142, and E151 in the HLA-C*03:02 binding groove and positions p3, p6, and p9 on the GY9 epitope are crucial in shaping and stabilizing the epitope binding. Our findings support the growing evidence of the contribution of HLA-C molecules to HIV-1 control and provide a prospect for vaccine strategies.

The work presented in this paper represents a preliminary study on the performance of the new Silicon tracker layer, the Layer 0 (L0), that will be installed on top of the Alpha Magnetic Spectrometer (AMS-02), at the end of 2024. AMS-02 is a cosmic rays (CR) detector that has been operating on the International Space Stations (ISS) since May 2011. Thanks to its 9-layer Silicon tracker, this apparatus can perform high energy CR measurements with an unprecedented level of statistics and precision. However, high Z (Z $\ge 15$) CR nuclei statistic is strongly affected by fragmentation along the detector: with the installation of the new Silicon layer will be possible to achieve new unique high energy (TeV region) measures for those nuclei along with increased statistics for all nuclei up to Zinc. To achieve this, a Silicon ladder prototype, that will be part of the final Silicon layer, has been exposed to an ions test beam at the super-proton-synchrotron (SPS) of the CERN to characterize its charge resolution and the readout electronics. Preliminary results have shown a charge resolution of 10 $\%$ for nuclei up to Z=7.

Duchenne muscular dystrophy (DMD) is a debilitating and fatal genetic disease affecting 1/3500 boys globally, characterized by progressive muscle breakdown and eventual death with an average lifespan in the mid-late twenties. While no cure yet exists for DMD, gene and antisense therapies have been heavily explored in recent years to better treat this disease. Four antisense therapies have received conditional FDA approval, and many more exist in varying stages of clinical trials. These upcoming therapies often utilize novel drug chemistries to address limitations of existing therapies, and their development could herald the next generation of antisense therapy. This review article aims to summarize the current state of development for antisense-based therapies for the treatment of Duchenne muscular dystrophy, exploring candidates designed for both exon skipping and gene knockdown.