Although HIV in the Middle East and North Africa is currently characterized as a low seroprevalence epidemic, there are numerous factors that are present in the region that could prevent—or exacerbate—the epidemic. The time to invest substantially in prevention—and gender-specific prevention in particular—is now. Given that most policy makers do not make gender-specific plans as epidemics progress, our research team—which draws upon expertise from both within and outside the region—worked together to make programmatic and policy suggestions in the Middle East and North Africa region in 5 key areas: (1) gender-specific and gender transformative HIV prevention interventions; (2) access to quality education and improvements in life skills and sex education; (3) economic empowerment; (4) property rights; and (5) antiviolence. In short, this work builds upon many ongoing efforts in the region and elucidates some of the links between gendered empowerment and health outcomes around the world, particularly HIV and AIDS.
Background Respiratory syncytial virus (RSV) is a public health burden; no vaccine is currently available. An mRNA-based RSV vaccine (mRNA-1345) encoding the RSV prefusion stabilized F (preF) glycoprotein is under clinical investigation. Methods A phase 1, randomized, observer-blind, placebo-controlled, dose-ranging study assessed safety and immunogenicity of mRNA-1345 in younger adults (YA; 18-49 years) and older adults (OA; 65-79 years) (NCT04528719). YA and OA were randomized to receive 1 dose of mRNA-1345 (50, 100, or 200 µg) or placebo. Results In all, 74 YA participants (mRNA-1345, n=19-20; placebo, n=15) and 202 OA participants (mRNA-1345, n=47-48; placebo, n=59) received study injections. mRNA-1345 was well-tolerated in both groups, with lower reactogenicity observed in OA vs YA at higher doses. Injection site pain was the most frequent local solicited adverse reaction (SAR, YA: mRNA-1345, 73.7-100%; placebo, 0%; OA: mRNA-1345, 61.7-78.7%; placebo, 12.7% [Fig 1]). Erythema and swelling were less frequent (mRNA-1345: YA, 5.3-15.0%; OA, 0-4.3%; and YA, 5.0-15.0%; OA, 2.1-4.3%; respectively vs placebo 0% for all). Overall, 57.9-100% (YA) and 53.2-78.7% (OA) of mRNA-1345 and 40.0% (YA) and 45.5% (OA) of placebo groups reported ≥ 1 systemic SAR, most commonly headache, fatigue, myalgia, and arthralgia. As expected, neutralizing antibodies (nAbs) were present at baseline (BL; Fig 2); mRNA-1345 significantly boosted antibody titers through month (M) 1 in YA and OA, with comparable immunogenicity observed across age groups. M1 geometric mean fold rise (GMFR) for RSV-A nAbs were 20.0-22.3 (YA) and 12.1-16.6 (OA) and for RSV-B, nAbs were 11.7-14.4 (YA) and 8.7-12.6 (OA). M1 PreF binding antibody (bAb) GMFRs were 16.1-21.7 (YA) and 8.4-12.1 (OA; Fig 3). Peak antibody titers declined through M6, but levels remained ≥ 4.1-fold above BL with minimal dose response. M6 GMFR for RSV-A nAbs were 7.0-9.6 (YA) and 4.1-5.8 (OA) and for RSV-B, nAbs were 5.0-8.9 (YA) and 4.5-5.5 (OA). M6 PreF bAbs GMFR were 5.9-7.0 (YA) and 4.1-4.7 (OA). Antibody decline over time was comparable in YA and OA cohorts. Conclusion mRNA-1345 is well-tolerated in YA and OA. Antibody levels were boosted substantially above BL through M6 in both cohorts. These data support the continued development of mRNA-1345 as an RSV vaccine. Disclosures Grace L. Chen, MD, MPH, Moderna, Inc.: Salary|Moderna, Inc.: Stocks/Bonds Runa Mithani, PharmD, Moderna, Inc.: Salary|Moderna, Inc.: Stocks/Bonds Archana Kapoor, PhD, Moderna, Inc.: Salary|Moderna, Inc.: Stocks/Bonds Sophia Lu, PhD, Moderna, Inc.: Salary|Moderna, Inc.: Stocks/Bonds Laila El Asmar, PhD, Moderna, Inc.: Salary|Moderna, Inc.: Stocks/Bonds Catherine A. Panozzo, PhD, Moderna, Inc.: Salary|Moderna, Inc.: Stocks/Bonds Christine A. Shaw, PhD, Moderna, Inc.: Salary|Moderna, Inc.: Stocks/Bonds Sonia K. Stoszek, PhD, Moderna, Inc.: Salary|Moderna, Inc.: Stocks/Bonds Allison August, MD, Moderna, Inc.: Salary|Moderna, Inc.: Stocks/Bonds.
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in Wiley Online Library (wileyonlinelibrary.com).Some novel [1,2,4]triazolo [3,4-b] [1,3,4]thiadiazole derivatives were synthesized from aryl acetic acids. All the synthesized derivatives were selected for the screening of antibacterial potential against Grampositive bacteria [Staphylococcus aureus (MTCC 3160) and Micrococcus luteus (MTCC 1538)] and Gram-negative bacteria [Escherichia coli (MTCC 1652) and Pseudomonas aeruginosa (MTCC 424)] and antifungal potential against Aspergillus niger (MTCC 8652) and Candida albicans (MTCC 227), and free radical scavenging activity through 2,2-diphenyl-2-picrylhydrazyl hydrate method. The compounds TH-4, TH-13, and TH-19 were found to be more potent antimicrobial agents compared to standard drugs. The compounds TH-3, TH-9, and TH-18 also showed significant antimicrobial activity. The compound TH-13 showed antioxidant activity with IC 50 value better than the standard compound. The structures of all the synthesized compounds were confirmed by Fourier transform infrared, 1 H-NMR, liquid chromatography-mass spectrometry, and CHN analyzer.
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