Background: Respiratory syncytial virus (RSV) is an important cause of lower respiratory tract illness (LRTI) in older adults. RSV prefusion F (RSVpreF) is a bivalent stabilized prefusion F vaccine containing RSV-A and RSV-B antigens. In this phase 3 trial in persons aged ≥60 years, RSVpreF demonstrated vaccine efficacy (VE) of 88.9% and 77.8% against RSV-associated LRTI with ≥3 symptoms at the end of RSV seasons 1 and 2, respectively. We describe final safety and efficacy results and present immunogenicity data. Methods: This study was conducted over 2 RSV seasons. Participants were randomized (1:1) to RSVpreF 120-µg or placebo. A secondary objective was to describe RSVpreF immunogenicity 1 month post-vaccination and before season 2 visits in participants from the United States and Japan. Results: One-month post-vaccination neutralization titer geometric mean fold rise (GMFR) was 12.1 for combined RSV-A/RSV-B. Geometric mean titers decreased at the preseason 2 visit but remained substantially higher than baseline (RSV-A/RSV-B GMFR = 4.7). One month post-vaccination, GMFRs for RSV-A/RSV-B neutralizing responses were 12.0 to 13.0 for subgroups stratified by age (60–69, 70–79, ≥80 years). RSV-A/RSV-B GMFRs in participants with prespecified chronic conditions were generally similar to those without (range, 11.4–14.4). A consistent favorable safety profile and durable VE were seen through 2 RSV seasons. Conclusions: High RSV neutralizing titers were observed 1 month after RSVpreF vaccination in persons aged ≥60 years, with similarly robust responses across subgroups. These immune responses corresponded with high RSVpreF VE against RSV-associated LRTI. RSVpreF had a favorable safety profile over 2 seasons. Clinical Trials Registration. NCT05035212; EudraCT, 2021-003693-31.

Individuals with certain chronic medical conditions are at higher risk of developing pneumonia and pneumococcal disease than those without. Using data from the Community-Acquired Pneumonia Immunization Trial in Adults (CAPiTA), this post hoc analysis assessed the efficacy of the 13-valent pneumococcal conjugate vaccine (PCV13) in adults aged ≥65 years with at-risk conditions. The Community-Acquired Pneumonia Immunization Trial in Adults (CAPiTA) was a double-blind, parallel-group, randomized, placebo-controlled study in the Netherlands in which adults aged ≥65 years received either PCV13 or placebo. Outcomes of interest were identified using prespecified clinical criteria, radiographic confirmation, routine microbiologic testing, and a serotype-specific urinary antigen detection assay. In this post hoc analysis, participants were classified by at-risk status based on self-reporting of any of the following chronic medical conditions: heart disease, lung disease, asthma, diabetes, liver disease, and smoking. The objective of this analysis was to assess PCV13 vaccine efficacy (VE) against a first episode of vaccine-serotype community-acquired pneumonia (VT-CAP) in at-risk participants. Of the 84,496 adults enrolled in the study, 41,385 (49.2%) were considered at risk owing to chronic medical conditions. Of the 139 VT-CAP cases, 115 (82.7%) occurred in these participants. VE of PCV13 against a first episode of VT-CAP among participants with at-risk conditions was 40.3% (95.2% CI: 11.4%, 60.2%). Average duration of follow-up since vaccination was 3.95 years for at-risk participants; protection did not wane over the study period. This post hoc analysis of the Community-Acquired Pneumonia Immunization Trial in Adults (CAPiTA) showed significant and persistent efficacy of PCV13 against VT-CAP in at-risk older adults. ClinicalTrials.gov identifier: NCT00744263.

Neisseria meningitidis serogroup B (MnB) is a significant cause of invasive meningococcal disease, but no broadly protective vaccine is yet approved. We assessed the safety and immunogenicity of a bivalent MnB vaccine composed of lipidated subfamily A and B variants of recombinant LP2086 (rLP2086, also known as factor H binding protein, fHBP). Forty-eight adults, ages 18–40 y, were randomized to receive 60, 120 or 200 μg of the bivalent rLP2086 vaccine or control at 0, 2 and 6 mo. Immunogenicity was assessed by rLP2086-specific immunoglobulin G (IgG) geometric mean titers for subfamily A and B proteins. Safety was determined by laboratory assessments of blood and urine and by reporting of solicited and unsolicited adverse events (AEs). The bivalent rLP2086 vaccine elicited high IgG titers following the second and third vaccination at all dose levels. In each of the four study arms, 11 of the 12 participating subjects reported ≥ 1 AE, and no serious AEs were reported. Local and systemic reactions were mainly mild to moderate. Laboratory abnormalities (including increased sodium, decreased neutrophils, and proteinuria) were not associated with clinical events and were not considered to be related to the study vaccine. Vaccinations were generally well-tolerated. Strong IgG antibody responses and the absence of clinically significant laboratory abnormalities support further development of the bivalent rLP2086 vaccine (www.clinicaltrials.gov; identifier: NCT00879814).

Background: Older individuals and adults with certain chronic or immunocompromising health conditions are at increased risk of severe respiratory syncytial virus (RSV) disease. Methods: In this phase 3 randomized trial of RSVpreF safety and immunogenicity in 18–59-year-olds at high risk of severe RSV disease, participants were randomized 2:1 to 1 RSVpreF (120 µg) or placebo dose. Primary safety endpoints included reactogenicity events and adverse events (AEs) through 7 days and 1 month after vaccination, respectively, and serious AEs (SAEs) and newly diagnosed chronic medical conditions (NDCMCs) throughout the study. In primary analyses, immunogenicity elicited 1 month after RSVpreF was bridged to a randomly selected subset of ≥60-year-olds receiving RSVpreF from the immunogenicity subset in the pivotal phase 3 RENOIR trial, which demonstrated RSVpreF efficacy. Noninferiority was declared if 95% confidence interval (CI) lower bounds were >.667 (neutralizing titer adjusted geometric mean ratios) and >−10% (seroresponse rate differences) for RSV-A and RSV-B. Results: Overall, 678 participants received RSVpreF (n = 453) or placebo (n = 225). Most reactogenicity events were mild/moderate; severe events occurred in ≤2.0% of participants overall. AE frequencies were similar in RSVpreF (7.1%) and placebo recipients (7.6%). No vaccine-related SAEs or NDCMCs were reported. One month after RSVpreF administration, noninferiority criteria were met in 18–59-year-olds versus ≥60-year-olds for RSV-A and RSV-B neutralizing titers and seroresponse rates. Conclusions: RSVpreF was well tolerated with no safety concerns and demonstrated immunobridging to efficacy in 18–59-year-olds at high risk of severe RSV disease versus ≥60-year-olds in whom efficacy was previously demonstrated, supporting use of RSVpreF to prevent RSV-associated disease in this population. NCT05842967.

Background/Objectives: Individuals with immunocompromising conditions are at high risk of developing severe respiratory syncytial virus (RSV) illness. This phase 3, single-arm study assessed the safety and immunogenicity of the bivalent RSV prefusion F protein−based (RSVpreF) 120-µg vaccine in immunocompromised and renally impaired adults. Methods: Participants were stratified by age group (18−<60-year-olds; ≥60-year-olds) and received two RSVpreF doses 1 month apart (i.e., Dose 1 and Dose 2, respectively). Reactogenicity events were collected for 7 days after each dose; adverse events through 1 month after the last dose; and serious adverse events, adverse events of special interest, and newly diagnosed chronic medical conditions throughout the study. Results: One month after Dose 1, RSVpreF elicited robust immune responses overall and across age and immunocompromised subgroups. Overall, geometric mean fold rises from before to 1 month after Dose 1 were high for RSV A and RSV B (8.3 and 9.0, respectively); no additional increases 1 month after Dose 2 (7.5 and 7.8) were observed. The most frequent local reaction was pain at the injection site, which was more common after Dose 2 than after Dose 1. The most frequent systemic event after any dose was fatigue. Most local reactions and systemic events were mild or moderate in severity. Adverse event and serious adverse event rates were 13.5% and 7.3% among 18−<60-year-olds and 22.4% and 14.0% among ≥60-year-olds, respectively. Conclusions: A single dose of the RSVpreF vaccine conferred robust immune responses in immunocompromised and renally impaired adults with no safety concerns. (ClinicalTrials.gov Identifier: NCT05842967).