Immunogenicity and Safety of a Third COVID-19 BNT162b2 mRNA Vaccine Dose in 5- to 11-Year Olds

In this ongoing study, substantially increased ancestral SARSCoV-2 neutralizing responses were observed 1 month after a third 10-µg BNT162b2 dose given to 5 to 11-year olds versus neutralizing responses post-dose 2. After dose 3, increased neutralizing responses against Omicron BA.1 and BA.4/BA.5 strains were also observed. The safety/tolerability profile was acceptable.Peer reviewe

Immunogenicity of a 20-valent pneumococcal conjugate vaccine in adults 18 to 64 years old with medical conditions and other factors that increase risk of pneumococcal disease

The aim of this post hoc analysis was to describe the immunogenicity of the 20-valent pneumococcal conjugate vaccine (PCV20) in adults with chronic medical conditions or smoking that place them at increased risk of developing pneumococcal disease. Data from 2 phase 3, randomized, active-controlled, double-blind studies in pneumococcal vaccine-naive adults were analyzed. Study 1: adults ≥18 years were enrolled in 1 of 3 age-based cohorts (18‒49, 50‒59, and ≥60 years) and randomized (1:1, adults ≥60 years; 3:1, younger cohorts) to receive 1 dose of PCV20 or 13-valent PCV (PCV13). Participants ≥60 years who received PCV13 were administered 23-valent polysaccharide vaccine 1 month later. Study 2: adults 18‒49 years were randomized (2:2:2:1) to receive 1 dose of PCV20 from 1 of 3 lots or PCV13. Opsonophagocytic activity (OPA) titers were measured in sera collected before and 1 month after vaccination. We investigated immune responses of PCV20 among participants 18‒64 and 18‒49 years of age with ≥1 medical condition or other factor (smoking) that increases the risk of serious pneumococcal disease. Of 4369 participants overall (PCV20, n = 2975; PCV13, n = 1394), 1329 participants (30%) had ≥1 risk factor; most commonly smoking, diabetes, and chronic pulmonary disease. Among participants with risk factors, substantial increases in OPA geometric mean titers were observed across the 20 vaccine serotypes from before vaccination to 1 month after PCV20. Robust immune responses to all 20 vaccine serotypes 1 month after PCV20 were observed in adults with increased risk of serious pneumococcal disease. Clinical trial registration NCT03760146, NCT03828617

Serum Troponin I Assessments in 5- to 30-Year-Olds After BNT162b2 Vaccination.

INTRODUCTION: Rare myocarditis and pericarditis cases have occurred in coronavirus disease 2019 (COVID-19) messenger RNA (mRNA) vaccine recipients. Troponin levels, a potential marker of myocardial injury, were assessed in healthy participants before and after BNT162b2 vaccination. METHODS: Vaccine-experienced 12- to 30-year-olds in phase 3 crossover C4591031 Substudy B (NCT04955626) who had two or three prior BNT162b2 30-μg doses were randomized to receive BNT162b2 30 μg followed by placebo, or placebo followed by BNT162b2 30 µg, 1 month apart. A participant subset, previously unvaccinated against COVID-19, in the phase 3 C4591007 study (NCT04816643) received up to three vaccinations (BNT162b2 10 μg or placebo [5- to 11-year-olds]) or open-label BNT162b2 30 μg (12- to 15-year-olds). Blood samples collected pre-vaccination, 4 days post-vaccination, and 1-month post-vaccination (C4591031 Substudy B only) were analyzed. Frequencies of elevated troponin I levels (male, > 35 ng/l; female, > 17 ng/l) were assessed. RESULTS: Percentages of 12- to 30-year-olds (n = 1485) in C4591031 Substudy B with elevated troponin levels following BNT162b2 or placebo receipt were 0.5% and 0.8% before vaccination, 0.7% and 1.0% at day 4, and 0.7% and 0.5% at 1 month, respectively. In Study C4591007 (n = 1265), elevated troponin I levels were observed in 0.2, 0.4, and 0.2% of 5- to 11-year-old BNT162b2 recipients at baseline and 4 days post-dose 2 and 3, respectively; corresponding values in 12- to 15-year-olds were 0.4, 0.4, and 0.7%. No 5- to 11-year-old placebo recipients had elevated troponin levels. No myocarditis or pericarditis cases or deaths were reported. CONCLUSIONS: Among 5- to  < 30-year-olds in both studies, troponin levels were rarely elevated (≤ 1.0%) and similar before and post-vaccination; troponin levels were also similar between BNT162b2 and placebo in 12- to 30-year-old and 5- to 11-year-old recipients in the respective studies. No myocarditis or pericarditis cases were reported. These findings did not provide evidence that BNT162b2 causes troponin elevations. No utility of routine measurement of troponin levels in asymptomatic BNT162b2 recipients was identified

Efficacy of a 4-Antigen Staphylococcus aureus Vaccine in Spinal Surgery: The STRIVE Randomized Clinical Trial

Staphylococcus aureus is a global pathogen frequently responsible for healthcare-associated infections, including surgical site infections (SSIs). Current infection prevention and control approaches may be limited, with S aureus antibiotic resistance remaining problematic. Thus, a vaccine to prevent or reduce S aureus infection is critically needed. This study evaluated efficacy and safety of an investigational 4-antigen S aureus vaccine (SA4Ag) in adults undergoing elective open posterior spinal fusion procedures with multilevel instrumentation. In this multicenter, site-level, randomized, double-blind trial, subjects 18-85 years old received a single dose of SA4Ag or placebo 10-60 days before surgery. SA4Ag efficacy in preventing postoperative S aureus bloodstream infection and/or deep incisional or organ/space SSI was the primary endpoint. Safety evaluations included local reactions, systemic events, and adverse events (AEs). Immunogenicity and colonization were assessed. Study enrollment was halted when a prespecified interim efficacy analysis met predefined futility criteria. SA4Ag showed no efficacy (0.0%) in preventing postoperative S aureus infection (14 cases in each group through postoperative Day 90), despite inducing robust functional immune responses to each antigen compared with placebo. Colonization rates across groups were similar through postoperative Day 180. Local reactions and systemic events were mostly mild or moderate in severity, with AEs reported at similar frequencies across groups. In patients undergoing elective spinal fusion surgical procedures, SA4Ag was safe, well tolerated, but despite eliciting substantial antibody responses that blocked key S aureus virulence mechanisms, was not efficacious in preventing S aureus infection. ClinicalTrials.gov: NCT02388165