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Background Protection against contemporary severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants requires sequence-adapted vaccines. Methods In this ongoing phase 2/3 trial, 12–17-year-olds (n = 108), 18–55-year-olds (n = 313), and >55-year-olds (n = 306) who previously received 3 original BNT162b2 30-µg doses, received a fourth dose (second booster) of 30-µg bivalent original/Omicron-BA.4/BA.5-adapted BNT162b2 (BNT162b2-Omi.BA.4/BA.5). For comparisons with original BNT162b2, participants were selected from another phase 3 trial. Immunologic superiority 1 month after vaccination, with respect to 50% neutralizing titers (lower bound [LB] of 2-sided 95% confidence interval [CI] for geometric mean ratio [GMR], >1), and noninferiority with respect to seroresponse rates (LB of 2-sided 95% CI for rate difference, greater than −5%), for Omicron BA.4/BA.5 were assessed in >55-year-olds versus original BNT162b2 as a second booster. Noninferiority with respect to neutralizing titer level (LB of 2-sided 95% CI for GMR, > 0.67) and seroresponse rate (LB of 2-sided 95% CI for rate difference, greater than −10%) of Omicron BA.4/BA.5 immune response for BNT162b2-Omi.BA.4/BA.5 in 18–55 versus >55-year-olds was assessed. Results One month after vaccination in >55-year-olds, the model-adjusted GMR of Omicron BA.4/BA.5 neutralizing titers for the BNT162b2-Omi.BA.4/BA.5 versus BNT162b2 groups (2.91 [95% CI, 2.45–3.44]) demonstrated the superiority of BNT162b2-Omi.BA.4/BA.5. Adjusted difference in the percentages of >55-year-olds with seroresponse (26.77% [95% CI, 19.59–33.95]) showed noninferiority of BNT162b2-Omi.BA.4/BA.5 to BNT162b2. Noninferiority of BNT162b2-Omi.BA.4/BA.5 in 18–55-year-olds compared with >55-year-olds was met for model-adjusted GMR and seroresponse. Geometric mean titers in 12–17-year-olds increased from baseline to 1 month after vaccination. The BNT162b2-Omi.BA.4/BA.5 safety profile was similar to the profiles for booster doses of bivalent Omicron BA.1-modified BNT162b2 and original BNT162b2 reported in previous studies. Conclusions Based on immunogenicity and safety data up to 1 month after vaccination in participants who previously received 3 original BNT162b2 doses, a BNT162b2-Omi.BA.4/BA.5 30-µg booster has a favorable benefit-risk profile. Clinical Trials Registration NCT05472038 [ABSTRACT FROM AUTHOR]

Background Respiratory syncytial virus (RSV) and influenza are both typically seasonal diseases, with winter peaks in temperate climates. Coadministration of an RSV vaccine and influenza vaccine could be a benefit, requiring 1 rather than 2 visits to a healthcare provider for individuals receiving both vaccines. Methods The primary immunogenicity objective of this phase 3, 1:1 randomized, double-blind, placebo-controlled study in healthy adults aged ≥65 years in Australia was to demonstrate noninferiority of immune responses with coadministration of the stabilized RSV prefusion F protein–based vaccine (RSVpreF) and seasonal inactivated influenza vaccine (SIIV) versus SIIV or RSVpreF administered alone, using a 1.5-fold noninferiority margin (lower bound 95% confidence interval >.667). Safety and tolerability were evaluated by collecting reactogenicity and adverse event data. Results Of 1403 participants randomized, 1399 received vaccinations (median age, 70; range, 65‒91 years). Local reactions and systemic events were mostly mild or moderate when RSVpreF was coadministered with SIIV or administered alone. No vaccine-related serious adverse events were reported. Geometric mean ratios were 0.86 for RSV-A and 0.85 for RSV-B neutralizing titers at 1 month after RSVpreF administration and 0.77 to 0.90 for strain-specific hemagglutination inhibition assay titers at 1 month after SIIV. All comparisons achieved the prespecified 1.5-fold noninferiority margin. Conclusions The primary study objectives were met, demonstrating noninferiority of RSVpreF and SIIV immune responses when RSVpreF was coadministered with SIIV and that RSVpreF had an acceptable safety and tolerability profile when coadministered with SIIV. The results of this study support coadministration of RSVpreF and SIIV in an older-adult population. Clinical Trials Registration https://clinicaltrials.gov/study/NCT05301322. [ABSTRACT FROM AUTHOR]

Background This phase 2 extension explored the long-term antibody persistence of an investigational Clostridioides difficile vaccine and the safety, tolerability, and immunogenicity of dose 4 approximately 12 months post–dose 3. Methods One year post–dose 3, healthy US 65- to 85-year-olds (N = 300) were randomized to dose 4 of vaccine at previously received antigen levels (100 or 200 μg) or placebo. Assessments included safety and percentages of participants achieving neutralizing antibody titers above prespecified thresholds (≥219 and ≥2586 neutralization units/mL for toxins A and B, respectively). Results In participants previously given three 200-µg doses and placebo in the extension, toxin A and B neutralizing antibodies were above prevaccination levels 48 months post–dose 3 (36 months after placebo); 24.0% and 26.0% had toxin A and B antibodies at or above prespecified thresholds, respectively. Neutralizing antibodies increased post–dose 4 (12 months post–dose 3) and persisted to 36 months post–dose 4. Thirty days post–dose 4, all participants had toxin A and 86.5% to 100% had toxin B titers at or above prespecified thresholds. Local reactions were more frequent in vaccine recipients. Systemic and adverse event frequencies were similar across groups. Conclusions C difficile vaccine immune responses persisted 48 months post–dose 3. Dose 4 was immunogenic and well tolerated, supporting continued development. Clinical Trials Registration. ClinicalTrials.gov NCT02561195. [ABSTRACT FROM AUTHOR]

Background and Objectives: The 20-valent pneumococcal conjugate vaccine (PCV20) was developed to expand protection for pneumococcal disease. It contains all 13-valent pneumococcal conjugate vaccine (PCV13) components plus conjugates for 7 additional serotypes. Our primary objective with this study was to evaluate PCV20 tolerability and safety., Methods: In this phase 3, multi-country, double-blind study, healthy infants born at ≥34 weeks' gestation were randomly assigned 2:1 to receive PCV20 or PCV13 at 2, 4, 6, and 12 to 15 months of age. Safety assessments included local reactions and systemic events within 7 days after each vaccination, adverse events (AEs) from dose 1 to 1 month after dose 3 and from dose 4 to 1 month after dose 4, and serious AEs and newly diagnosed chronic medical conditions from dose 1 through 6 months after the last dose., Results: Participants received PCV20 (N = 1000) or PCV13 (N = 504); 91.7% received all 4 doses. The frequencies of local reactions and systemic events were generally similar in PCV20 and PCV13 groups, with most reported as mild or moderate. The most common local reaction was injection site pain (PCV20, 24.7% to 40.5%; PCV13, 26.8% to 42.0%); irritability was the most common systemic event (PCV20, 54.8% to 68.2%; PCV13, 54.7% to 68.5%). AE frequencies were similar in both groups. No serious AEs were related to study vaccines. Few newly diagnosed chronic medical conditions were reported (2.8% in both groups). PCV20 was safe across multiple countries, in late preterm infants, and when administered with other vaccines., Conclusions: A 4-dose series of PCV20 had a tolerability and safety profile similar to that of PCV13., Competing Interests: CONFLICT OF INTEREST DISCLOSURES: Drs Hajdu and Hughes have indicated they have no potential conflicts of interest relevant to this article to disclose. All other authors are employees or former employees of Pfizer and may hold stock or stock options.

Background: Clostridioides difficile infection (CDI) causes substantial mortality and healthcare burden. We assessed the detoxified toxin-A/B PF-06425090 vaccine for primary CDI prevention., Methods: This phase 3 observer-blinded study randomized (1:1) ≥50-year-olds at increased CDI risk (N=17,535) to receive 3 PF-06425090 or placebo doses (0,1,6-months). Primary endpoints were first CDI episode (≥3 unformed stools within 24 hours; central laboratory-confirmed toxin A/B positive) ≥14 days post-dose 3 (PD3; first primary) and post-dose 2 (PD2; second primary). CDI duration, need for CDI-related medical attention (secondary endpoints), and antibiotic use (post hoc analysis) PD3 were evaluated. Tolerability/safety was assessed., Results: The primary endpoint was not met (17 PF-06425090 and 25 placebo recipients had first CDI episode ≥14 days PD3 [vaccine efficacy (VE)=31.0% (96.4%CI: -38.7%-66.6%)]; 24 PF-06425090 and 34 placebo recipients had first CDI episode ≥14 days PD2 [VE=28.6% (-28.4%-61.0%)]). Median CDI duration was lower with PF-06425090 (1 day) versus placebo (4 days; 2-sided nominal P=0.02). Of participants with first CDI episode, 0 PF-06425090 and 11 placebo recipients sought CDI-related medical attention (post hoc analysis estimated VE=100% [95%CI: 59.6%-100.0%]) and 0 PF-06425090 and 10 placebo recipients required antibiotic treatment (VE=100% [54.8%-100.0%]). Local reactions were more frequent in PF-06425090 recipients and systemic events were generally similar between groups; most were mild-to-moderate. AE rates were similar between groups., Conclusions: Three PF-06425090 doses were safe and well-tolerated. Although the primary endpoint was not met, PF-06425090 reduced symptom duration, CDI requiring medical attention, and CDI-directed antibiotic treatment, highlighting its potential to reduce CDI-associated healthcare burden. NCT03090191., (© The Author(s) 2024. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)