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Concomitant administration may improve vaccination rates. This analysis of a phase 1/2 randomized study included 1073 healthy ≥65-year-olds who previously received ≥3 mRNA COVID-19 vaccine doses. Participants received concomitantly administered RSVpreF and bivalent BA.4/BA.5-adapted BNT162b2 vaccine (concomitant administration) with or without quadrivalent influenza vaccine (QIV), admixed combined RSVpreF + BNT162b2 vaccine (combined vaccine) with or without QIV, RSVpreF, BNT162b2, or QIV. Immunogenicity objectives included demonstrating the noninferiority of neutralizing antibody titers elicited by concomitant administration and combined vaccine compared with RSVpreF or BNT162b2 administered alone, and by concomitant administration and combined vaccine given with QIV compared with RSVpreF, BNT162b2, and QIV alone. Reactogenicity (≤7 days) and safety ≤1 month (adverse events (AEs)) and ≤6 months (serious AEs (SAEs)) after vaccination were assessed. Noninferiority for all immunogenicity comparisons was demonstrated. All vaccine groups were well tolerated; no new safety concerns were identified. Reactogenicity was mostly mild/moderate with rates generally similar across groups, except injection site pain and fatigue, which were less frequent with RSVpreF + placebo vs. other groups. AEs were infrequent, mostly mild/moderate, occurring at similar frequencies across groups. No AEs leading to study withdrawal or vaccine-related SAEs were reported. Favorable safety and tolerability alongside similar immunogenicity provide support for concomitant or combined use of RSVpreF and BNT162b2, with or without QIV, to help protect older adults from these important respiratory pathogens (NCT05886777).

Background : Respiratory syncytial virus (RSV) infections usually cause mild, cold-like symptoms in most people, but are a leading infectious disease causing infant death and hospitalization and can result in increased morbidity and mortality in older adults and at-risk individuals. Pfizer has developed Abrysvo ® , an unadjuvanted bivalent recombinant protein subunit vaccine containing prefusion-stabilized fusion (F) proteins representing RSV A and RSV B subgroups (RSVpreF). It is the only RSV vaccine approved for both maternal immunization to protect infants and active immunization of older adults (≥60 years) and 18-59-year-old individuals with high-risk conditions for prevention of RSV disease. Methods : Nonclinical safety studies, including a repeat-dose toxicity (RDT) study in rats and a combined developmental and reproductive toxicity (DART) study in rabbits, were conducted to support early clinical development. Study designs and parameters evaluated in these studies were consistent with principles and practices as outlined in relevant regulatory guidelines. RSVpreF bivalent vaccine, with or without Al(OH) 3 , was administered intramuscularly (IM) at 2× the human dose to animals in both studies. Results : Locally tolerated, reversible, inflammatory responses at the injection sites and the draining lymph nodes were observed as typical findings following vaccination. No effect of RSVpreF, with or without Al(OH) 3 , was observed on female fertility or on embryo-fetal or postnatal survival, growth, or development in the DART study. In both studies, robust immune responses to both RSV A and B antigens were observed, especially with the Al(OH) 3 formulation. Conclusions : RSVpreF was well-tolerated both locally and systemically without any adverse effects on reproductive and developmental endpoints.

Background: Respiratory syncytial virus (RSV) causes substantial respiratory disease. Bivalent RSV prefusion F (RSVpreF) vaccine is licensed in ≥60-year-olds. RSVpreF was well tolerated and immunogenic in a phase 1/2 study. We evaluated antibody persistence after initial vaccination and safety and immunogenicity after revaccination from this study., Methods: Healthy adults were randomized to receive initial vaccination and revaccination 12 months later with either placebo or RSVpreF (240 µg with or without aluminum hydroxide). RSV-A and RSV-B geometric mean neutralizing titers (GMTs) were measured through 12 months after both vaccinations. Tolerability and safety were assessed., Results: There were 263 participants revaccinated (18-49 years old, n = 134; 65-85 years old, n = 129). Among 18- to 49-year-olds and 65- to 85-year-olds, geometric mean fold rises (GMFRs) for both RSV subgroups (RSV-A, RSV-B) 1 month after initial RSVpreF vaccination were 13.3 to 20.4 and 8.9 to 15.5, respectively, as compared with levels before initial vaccination; corresponding GMFRs 12 months after initial vaccination were 4.1 to 5.0 and 2.6 to 4.1. GMFRs 1 month after revaccination vs levels before revaccination were 1.4 to 2.3 and 1.4 to 2.2 for 18- to 49-year-olds and 65- to 85-year-olds. Peak GMTs after revaccination were lower than those after initial vaccination. GMTs 12 months after initial vaccination and revaccination were similar, with GMFRs ranging from 0.7 to 1.6. No safety signals occurred., Conclusions: RSVpreF revaccination was immunogenic and well tolerated among adults. Clinical Trials Registration. NCT03529773 (ClinicalTrials.gov)., Competing Interests: Potential conflicts of interest. E. E. W. reports receiving grants from Pfizer, Merck Sharp and Dohme, and Janssen and serving in unpaid consultancy roles for Janssen, Merck, Moderna, and Pfizer. A. R. F. reports receiving grant funding from Pfizer Inc, Merck, Janssen, BioFire Diagnostics, Vax Co, and CyanVac and consulting fees from Gilead, GlaxoSmithKline, Icosavax, and Novavax. A. M. Z., Q. J., A. G., D. R., E. G., D. C., K. U. J., W. C. G., K. A. S., and B. S.-T. are current or former employees of Pfizer Inc and may hold stock or stock options. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2024. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

Background: Group B streptococcus is a major cause of neonatal disease. Natural history studies have linked maternally transferred anti-group B streptococcus capsular polysaccharide antibodies with protection against infant group B streptococcus disease. Previous studies of capsular polysaccharide antibody concentration in European populations have used maternal (not infant) sera and a non-standardised assay. This study aimed to evaluate anti-capsular polysaccharide IgG concentrations associated with protection against invasive group B streptococcus disease in Finnish infants., Methods: In this retrospective case-control study, we used cord sera from the Finnish DIPP study repository, which was obtained between Jan 1, 1995, and Dec 31, 2017. We included infants aged 6 months or younger with group B streptococcus infection (cases) and healthy infants (controls). We enrolled infants with invasive neonatal group B streptococcus (55 cases) and matched controls (229 controls) aged 6 months or younger after identification from Finnish health registers. We measured anti-capsular polysaccharide IgG (serotypes Ia-V) concentration using a standardised immunoassay and we estimated its relationship to disease risk using a Bayesian model. We used the derived risk-concentration curve to predict potential efficacy of six-valent group B streptococcus capsular polysaccharide vaccine (GBS6) based on previously reported immunogenicity data., Findings: Most (32 [58%] of 55 cases) group B streptococcus cases were due to serotype III and anti-serotype III streptococcus capsular IgG concentrations were higher in serotype III-matched controls than in cases (p<0·001). 0·120-0·266 μg/mL serotype III-specific IgG was estimated to confer 75-90% risk reduction against serotype III disease. A universal risk-concentration curve, aggregating results across all six serotypes, yielded similar results. Application of this curve to GBS6 immunogenicity data predicted maternal immunisation to be more than 80% efficacious for prevention of infant group B streptococcus disease., Interpretation: Higher neonatal anti-capsular polysaccharide serum IgG concentration at birth correlated with reduced risk of infant group B streptococcus disease in Finland. Based on these results, a maternal group B streptococcus capsular conjugate vaccine currently in development is predicted to be efficacious., Funding: Pfizer., Competing Interests: Declaration of interests DR, EG, NCS, BJ, ASA, and RS are employees of Pfizer and are recipients of stock options in Pfizer. ASA is an inventor on patents related to group B streptococcus vaccines. AS, MT, LL, and AAP are employees of the Finnish Institute for Health and Welfare, which has received research funding from Pfizer., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Background: Natural history studies have correlated serotype-specific anti-capsular polysaccharide (CPS) IgG in newborns with a reduced risk of group B streptococcal disease. A hexavalent CPS-cross-reactive material 197 glycoconjugate vaccine (GBS6) is being developed as a maternal vaccine to prevent invasive group B streptococcus in young infants., Methods: In an ongoing phase 2, placebo-controlled trial involving pregnant women, we assessed the safety and immunogenicity of a single dose of various GBS6 formulations and analyzed maternally transferred anti-CPS antibodies. In a parallel seroepidemiologic study that was conducted in the same population, we assessed serotype-specific anti-CPS IgG concentrations that were associated with a reduced risk of invasive disease among newborns through 89 days of age to define putative protective thresholds., Results: Naturally acquired anti-CPS IgG concentrations were associated with a reduced risk of disease among infants in the seroepidemiologic study. IgG thresholds that were determined to be associated with 75 to 95% reductions in the risk of disease were 0.184 to 0.827 μg per milliliter. No GBS6-associated safety signals were observed among the mothers or infants. The incidence of adverse events and of serious adverse events were similar across the trial groups for both mothers and infants; more local reactions were observed in the groups that received GBS6 containing aluminum phosphate. Among the infants, the most common serious adverse events were minor congenital anomalies (umbilical hernia and congenital dermal melanocytosis). GBS6 induced maternal antibody responses to all serotypes, with maternal-to-infant antibody ratios of approximately 0.4 to 1.3, depending on the dose. The percentage of infants with anti-CPS IgG concentrations above 0.184 μg per milliliter varied according to serotype and formulation, with 57 to 97% of the infants having a seroresponse to the most immunogenic formulation., Conclusions: GBS6 elicited anti-CPS antibodies against group B streptococcus in pregnant women that were transferred to infants at levels associated with a reduced risk of invasive group B streptococcal disease. (Funded by Pfizer and the Bill and Melinda Gates Foundation; C1091002 ClinicalTrials.gov number, NCT03765073.)., (Copyright © 2023 Massachusetts Medical Society.)

Background: Respiratory syncytial virus (RSV) causes substantial morbidity and mortality in older adults and adults with comorbidities. An effective vaccine is needed. An investigational bivalent prefusion F vaccine (RSVpreF) was assessed in healthy adults., Methods: This phase 1/2 study randomized adults 18-85 years old to receive placebo or 60, 120, or 240 µg RSVpreF (with or without aluminum hydroxide) alone or concomitantly with seasonal inactivated influenza vaccine (SIIV). Safety and immunogenicity were assessed., Results: In older adults, reactogenicity events were predominantly mild or moderate among RSVpreF recipients; adverse events through 1 month postvaccination were similar across formulations. Coadministration with SIIV did not appear to affect safety among younger or older adults. All RSVpreF formulations with or without concomitant SIIV elicited robust RSV serum-neutralizing responses in adults aged 50-85 years 1 month postvaccination. Neutralizing titers 1 and 12 months postvaccination were 6.9-14.9 and 2.9-4.5 times, respectively, those before vaccination. SIIV immune responses trended lower when coadministered with RSVpreF., Conclusions: RSVpreF formulations administered alone or with SIIV were well tolerated and highly immunogenic in older adults, supporting the potential for RSVpreF to protect older adults from RSV disease., Clinical Trials Registration: NCT03529773., (© The Author(s) 2021. Published by Oxford University Press for the Infectious Diseases Society of America.)

Background: Respiratory syncytial virus (RSV), a major cause of illness and death in infants worldwide, could be prevented by vaccination during pregnancy. The efficacy, immunogenicity, and safety of a bivalent RSV prefusion F protein-based (RSVpreF) vaccine in pregnant women and their infants are uncertain., Methods: In a phase 2b trial, we randomly assigned pregnant women, at 24 through 36 weeks' gestation, to receive either 120 or 240 μg of RSVpreF vaccine (with or without aluminum hydroxide) or placebo. The trial included safety end points and immunogenicity end points that, in this interim analysis, included 50% titers of RSV A, B, and combined A/B neutralizing antibodies in maternal serum at delivery and in umbilical-cord blood, as well as maternal-to-infant transplacental transfer ratios., Results: This planned interim analysis included 406 women and 403 infants; 327 women (80.5%) received RSVpreF vaccine. Most postvaccination reactions were mild to moderate; the incidence of local reactions was higher among women who received RSVpreF vaccine containing aluminum hydroxide than among those who received RSVpreF vaccine without aluminum hydroxide. The incidences of adverse events in the women and infants were similar in the vaccine and placebo groups; the type and frequency of these events were consistent with the background incidences among pregnant women and infants. The geometric mean ratios of 50% neutralizing titers between the infants of vaccine recipients and those of placebo recipients ranged from 9.7 to 11.7 among those with RSV A neutralizing antibodies and from 13.6 to 16.8 among those with RSV B neutralizing antibodies. Transplacental neutralizing antibody transfer ratios ranged from 1.41 to 2.10 and were higher with nonaluminum formulations than with aluminum formulations. Across the range of assessed gestational ages, infants of women who were immunized had similar titers in umbilical-cord blood and similar transplacental transfer ratios., Conclusions: RSVpreF vaccine elicited neutralizing antibody responses with efficient transplacental transfer and without evident safety concerns. (Funded by Pfizer; ClinicalTrials.gov number, NCT04032093.)., (Copyright © 2022 Massachusetts Medical Society.)

Background: Protection against human respiratory syncytial virus (RSV) remains an unmet need potentially addressable by maternal immunization. This phase 1/2 study evaluated a bivalent prefusion F vaccine (RSVpreF) with antigens from RSV subgroups A and B., Methods: Adults 18-49 years old (N = 618) were randomized to receive placebo or 60, 120, or 240 µg RSVpreF with or without Al(OH)3. Safety and immunogenicity were evaluated., Results: RSVpreF recipients more frequently reported local reactions and systemic events than placebo recipients; these were mostly mild or moderate. No vaccine-related serious adverse events occurred through 12 months postvaccination. All RSVpreF formulations induced 1-month postvaccination virus-neutralizing titers higher than those associated with protection of high-risk infants by palivizumab, the only prophylactic currently available for RSV. Geometric mean fold rises (GMFRs) across RSVpreF doses/formulations were 10.6-16.9 for RSV A and 10.3-19.8 for RSV B at 1 month postvaccination, greater than those historically elicited by postfusion F vaccines. GMFRs were 3.9-5.2 and 3.7-5.1, respectively, at 12 months postvaccination., Conclusions: RSVpreF formulations were safe, well tolerated, and induced robust neutralizing responses in adults. These findings support development of RSVpreF, which is being evaluated in a pivotal phase 3 study for maternal immunization., Clinical Trials Registration: NCT03529773., (© The Author(s) 2021. Published by Oxford University Press for the Infectious Diseases Society of America.)