BACKGROUND:Emergence of severe acute respiratory syndrome coronavirus 2 sublineages warrants the use of sequence-adapted vaccines to provide protection against coronavirus disease 2019. METHODS:In this phase 3 trial, adults 18‒55 years old who had previously received three 30 μg doses of BNT162b2 vaccine were randomized to receive a 60 or 30 μg dose of bivalent Omicron BA.1‒adapted BNT162b2 comprising equal amounts of ancestral and monovalent messenger RNA BA.1 (bivalent BA.1) or a 60 μg dose of monovalent Omicron BA.1‒adapted BNT162b2 (monovalent BA.1). Safety (local reactions, systemic events, adverse events [AEs], and serious AEs) was the primary objective. Exploratory analyses assessed immune responses against Omicron BA.1, BA.4, and BA.5 subvariants and ancestral strain. RESULTS:Among the 1054 randomized participants who received monovalent BA.1 or bivalent BA.1, frequencies of local reactions, systemic events, and AEs were slightly higher with 60 µg monovalent BA.1 than either bivalent BA.1 dose level. One month after vaccination, bivalent BA.1 (30 and 60 μg) and monovalent BA.1 (60 μg) induced substantial neutralizing responses against Omicron BA.1 (50% neutralizing titer geometric mean fold rises [GMFRs], 15.4 [95% CI 12.4-19.2], 17.1 [13.7-21.4], and 24.6 [19.3-31.4], respectively) and ancestral strain (GMFRs, 6.2 [5.1-7.6], 7.3 [6.0-8.9], and 7.0 [5.7-8.7], respectively). In a smaller (n = 30/treatment arm) sentinel cohort, all study vaccines modestly neutralized Omicron BA.4 and BA.5. CONCLUSIONS:Bivalent and monovalent BA.1‒adapted vaccines had a safety profile similar to the original BNT162b2 30 μg and induced substantial neutralizing responses against Omicron BA.1 and ancestral strains. CLINICAL TRIALS REGISTRATION:NCT04955626.

A human cytomegalovirus (CMV) vaccine to prevent congenital disease is a public health priority. We previously demonstrated that vaccine-elicited rhesus CMV (RhCMV) neutralizing titers and T-cell responses comparable to natural infection failed to protect from RhCMV infection after experimental oral challenge. Consequently, we established a natural transmission model in which newborn rhesus macaques are cohoused with their RhCMV-positive mothers and immunized 5 times between 0 and 24 months with glycoprotein B (gB), pentamer, pp65, and in 1 group viral interleukin 10. While no significant differences were observed in infection rate between the vaccine and placebo groups at 40 weeks after birth, partial protection was observed at week 52 (83.3% infection in placebo, 42.1%-50% in vaccine recipients). Within 14 weeks of juvenile macaques transfer to group housing, all shed RhCMV. These results suggest that the neonatal RhCMV natural transmission model may recapitulate observations in humans immunized with recombinant gB and can be a useful tool for evaluating CMV vaccine candidates. We present a neonatal rhesus macaque RhCMV transmission model, where newborns are cohoused with RhCMV-positive mothers before group housing. Evaluation of CMV vaccine candidates demonstrated partial protection at week 52, indicating the value of this model to predict transmission dynamics postvaccination.

Background:Vaccination during pregnancy to protect infants against respiratory syncytial virus (RSV) disease relies on transplacental transfer of RSV neutralizing antibodies. Observational natural history studies on correlations between RSV-specific antibody levels and infant protection have, however, had variable results. Methods:This observational natural history study characterized RSV-specific neutralizing antibody levels and described infant RSV disease dynamics in South African and United States (US) maternal-infant pairs. Naturally acquired RSV serum neutralizing titers were determined from 726 pregnant individuals and their infants at birth and assessed in relationship to serum neutralizing titers conferred by serum palivizumab protective levels. Results:In the absence of vaccination, we found no correlation between RSV neutralizing titers and infant protection against RSV-associated lower respiratory tract illness. South Africa versus US comparison revealed similar, broad distributions of maternal serum RSV neutralizing titers but lower transplacental transfer rates in South Africa (0.6 [95% confidence interval {CI}, .6-.7]) than the US (1.3 [95% CI, 1.1-1.4]) and high rates of community spread of infant asymptomatic RSV infection in South Africa versus the US. Conclusions:These findings suggest that the effectiveness of maternal immunization against infant RSV relies on immunization shifting natural distribution of maternal RSV neutralizing titers into the protective range for infants, which is supported by efficacy demonstrated with RSV maternal immunization.

BACKGROUND:A hexavalent group B streptococcus (GBS) polysaccharide conjugate vaccine (GBS6) is being developed to prevent invasive group B streptococcal disease in infants through active maternal immunisation. We previously reported results for GBS6 administered to non-pregnant adults (NCT03170609). Here, we aim to extend these results to determine safety and immunogenicity of a second dose of GBS6 in non-pregnant adults who received a primary dose of GBS6. METHODS:This phase 2, open-label extension of a phase 1/2 randomised controlled trial was done at four sites in the USA to assess the safety, tolerability, and immunogenicity of a booster dose (20 μg capsular polysaccharide per serotype per dose) of GBS6 formulated with and without aluminium phosphate (AlPO4). Healthy adults who were aged 18-49 years during participation in the phase 1/2 study approximately 2 years before and received one of the six GBS6 formulations were enrolled. Participants received a single dose of GBS6 20 μg capsular polysaccharide (CPS) per serotype on study day 1, with or without AlPO4 based on the formulation received in the phase 1/2 study. Primary endpoints evaluated GBS6 safety (in participants receiving one or more doses) based on solicited local reactions and systemic events within 14 days, adverse events within 1 month, and unsolicited serious adverse events and medically attended adverse events up to 6 months after vaccination. Secondary immunogenicity endpoints (in the evaluable population of participants in compliance with key protocol criteria) included assessments of GBS serotype-specific IgG geometric mean concentrations (GMCs) and geometric mean fold-rises (GMFRs) in serum samples collected at 1 month after versus before booster vaccination. This study is registered with ClinicalTrials.gov (NCT04258995). FINDINGS:Of 297 participants who completed the base study, 151 received the GBS6 booster dose (76 participants with and 75 without AlPO4) and were included in the safety analysis. The median time to booster from primary vaccination was 2·4 years (IQR 2·3-2·5). Most participants were women (114 [75%] of 151) and White (125 [83%] of 151). The mean age was 36·7 years (SD 8·67). Pain at the injection site was the most frequently reported solicited local reaction (52 [68%] of 76 participants who received GBS6 with AlPO4 and 32 [43%] of 75 without AlPO4) and was severe in two (3%) of 76 participants who received GBS6 with AlPO4 and no participant who received the vaccine without adjuvant. Systemic events occurred at similar frequencies in both groups (45 [59%] of 76 with AlPO4 and 46 [61%] of 75 without AlPO4), and were mostly mild or moderate in severity. The number of participants reporting any type of unsolicited adverse event was low and similar for GBS6 with AlPO4 versus GBS6 without AlPO4 (11 [14%] of 76 vs 12 [16%] of 75). No adverse event was deemed to be related to GBS6. One serious adverse event, assessed as not related to the product being investigated, of thermal burn was reported in a participant who received GBS6 with AlPO4. Low rates of medically attended adverse events were reported in both groups of participants receiving a booster dose of GBS6 (nine [12%] of 76 with AlPO4 and seven [9%] of 75 without AlPO4). For all serotypes, serotype-specific anti-CPS IgG GMCs mostly waned over the 2-year period after the primary vaccination but remained elevated before the booster dose compared with before the primary dose of GBS6. A booster dose of GBS6 elicited robust GBS serotype-specific anti-CPS IgG responses that were two-fold to 18-fold higher 1 month after the booster dose (GMC range 6·025-60·304 μg/mL) than 1 month after the primary dose (0·365-35·173 μg/mL). Anti-CPS IgG GMFRs ranged from approximately ten-fold to 59-fold across the serotypes and formulations from before the booster dose (GMC range 0·130-5·274 μg/mL) to 1 month after the booster dose. INTERPRETATION:The results of this study showed that a single 20 μg booster dose of GBS6 given approximately 2 years after a primary dose to healthy, non-pregnant adults was safe and elicited robust immune responses that were consistently higher than those after the primary dose. As there is precedent for repeat doses of vaccines to augment or sustain circulating antibodies available for placental transfer with each pregnancy, results from this study might inform decisions around future dosing strategies for GBS6 for maternal immunisation with subsequent pregnancies should GBS6 be approved for use in pregnancy. FUNDING:Pfizer.

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, and 6 months). Primary end points 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 end points), and antibiotic use (post hoc analysis) PD3 were evaluated. Tolerability and safety were assessed. Results. The primary end point was not met (17 PF-06425090 and 25 placebo recipients had first CDI episode >= 14 days PD3 [vaccine efficacy (VE) = 31.0% (96.4% confidence interval [CI], -38.7% to 66.6%)]; 24 PF-06425090 and 34 placebo recipients had first CDI episode >= 14 days PD2 [VE = 28.6% (96.4% CI, -28.4% to 61.0%)]. Median CDI duration was lower with PF-06425090 (1 day) versus placebo (4 days; 2-sided nominal P =.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% to 100.0%) and 0 PF-06425090 and 10 placebo recipients required antibiotic treatment (VE = 100%; 95% CI, 54.8% to 100.0%). Local reactions were more frequent in PF-06425090 recipients, and systemic events were generally similar between groups; most were mild to moderate. Adverse event rates were similar between groups. Conclusions. Three PF-06425090 doses were safe and well tolerated. Although the primary end point was not met, PF-06425090 reduced symptom duration, CDI that required medical attention, and CDI-directed antibiotic treatment, highlighting its potential to reduce CDI-associated healthcare burden. Clinical Trials Registration. NCT03090191.

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.

Background/Objectives: Respiratory syncytial virus (RSV) is the leading cause of severe respiratory disease in infants worldwide. Maternal immunization to protect younger infants is supported by evidence that virus-neutralizing antibodies, which are efficiently transferred across the placenta from mother to fetus, are a primary immune mediator of protection. In maternal RSV vaccine studies, estimates of correlates of protection are elusive because many factors of maternal–fetal immunobiology and disease characteristics must be considered for the estimates. Methods: We developed statistical models that aims to predict vaccine efficacy (VE) in infants following maternal immunization by including quantifiable covariates of the antibody titer distribution of the mother (pre- and post-immunization), the transplacental transfer ratio of IgG antibodies, the rate of antibody decay, and RSV disease incidence rate, all of which are season- and time-dependent and vary by infant age. Result: Our model shows that integrating the lower respiratory tract disease risk based on infant airway diameter and associated airway resistance is critical to appropriately model predicted infant VE. The VE predictions by our models, which preceded maternal RSV prefusion F vaccine efficacy trial primary readouts, closely align with the VE outcomes of these field studies. Conclusion: Our models successfully predicted VE of the RSV maternal vaccines and have potential use in modeling the clinical trial out-comes of other respiratory disease vaccines where maternal antibodies play a role in the protection of newborns.

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).

Abstract Background Staphylococcus aureus is a global pathogen that is 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. We evaluated the efficacy and safety of an investigational 4-antigen S. aureus vaccine (SA4Ag) in adults undergoing elective open posterior spinal fusion procedures with multilevel instrumentation. Methods In this multicenter, site-level, randomized, double-blind trial, patients aged 18–85 years 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 SSIs was the primary end point. Safety evaluations included local reactions, systemic events, and adverse events (AEs). Immunogenicity and colonization were assessed. Results 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. Conclusions In patients undergoing elective spinal fusion surgical procedures, SA4Ag was safe and well tolerated but, despite eliciting substantial antibody responses that blocked key S. aureus virulence mechanisms, was not efficacious in preventing S. aureus infection. Clinical Trials Registration. NCT02388165.

Respiratory syncytial virus (RSV) is the leading, global cause of serious respiratory disease in infants and is an important cause of respiratory illness in older adults. No RSV vaccine is currently available. The RSV fusion (F) glycoprotein is a key antigen for vaccine development, and its prefusion conformation is the target of the most potent neutralizing antibodies. Here, we describe a computational and experimental strategy for designing immunogens that enhance the conformational stability and immunogenicity of RSV prefusion F. We obtained an optimized vaccine antigen after screening nearly 400 engineered F constructs. Through in vitro and in vivo characterization studies, we identified F constructs that are more stable in the prefusion conformation and elicit ~10-fold higher serum-neutralizing titers in cotton rats than DS-Cav1. The stabilizing mutations of the lead construct (847) were introduced onto F glycoprotein backbones of strains representing the dominant circulating genotypes of the two major RSV subgroups, A and B. Immunization of cotton rats with a bivalent vaccine formulation of these antigens conferred complete protection against RSV challenge, with no evidence of disease enhancement. The resulting bivalent RSV prefusion F investigational vaccine has recently been shown to be efficacious against RSV disease in two pivotal phase 3 efficacy trials, one for passive protection of infants by immunization of pregnant women and the second for active protection of older adults by direct immunization.

Investment, collaboration, and coordination have been key

Abstract Background Safe and effective vaccines against coronavirus disease 2019 (Covid-19) are urgently needed in young children. Methods We conducted a phase 1 dose-finding study and are conducting an ongoing phase 2–3 safety, immunogenicity, and efficacy trial of the BNT162b2 vaccine in healthy children 6 months to 11 years of age. We present results for children 6 months to less than 2 years of age and those 2 to 4 years of age through the data-cutoff dates (April 29, 2022, for safety and immunogenicity and June 17, 2022, for efficacy). In the phase 2–3 trial, participants were randomly assigned (in a 2:1 ratio) to receive two 3-μg doses of BNT162b2 or placebo. On the basis of preliminary immunogenicity results, a third 3-μg dose (≥8 weeks after dose 2) was administered starting in January 2022, which coincided with the emergence of the B.1.1.529 (omicron) variant. Immune responses at 1 month after doses 2 and 3 in children 6 months to less than 2 years of age and those 2 to 4 years of age were immunologically bridged to responses after dose 2 in persons 16 to 25 years of age who received 30 μg of BNT162b2 in the pivotal trial. Results During the phase 1 dose-finding study, two doses of BNT162b2 were administered 21 days apart to 16 children 6 months to less than 2 years of age (3-μg dose) and 48 children 2 to 4 years of age (3-μg or 10-μg dose). The 3-μg dose level was selected for the phase 2–3 trial; 1178 children 6 months to less than 2 years of age and 1835 children 2 to 4 years of age received BNT162b2, and 598 and 915, respectively, received placebo. Immunobridging success criteria for the geometric mean ratio and seroresponse at 1 month after dose 3 were met in both age groups. BNT162b2 reactogenicity events were mostly mild to moderate, with no grade 4 events. Low, similar incidences of fever were reported after receipt of BNT162b2 (7% among children 6 months to <2 years of age and 5% among those 2 to 4 years of age) and placebo (6 to 7% among children 6 months to <2 years of age and 4 to 5% among those 2 to 4 years of age). The observed overall vaccine efficacy against symptomatic Covid-19 in children 6 months to 4 years of age was 73.2% (95% confidence interval, 43.8 to 87.6) from 7 days after dose 3 (on the basis of 34 cases). Conclusions A three-dose primary series of 3-μg BNT162b2 was safe, immunogenic, and efficacious in children 6 months to 4 years of age. (Funded by BioNTech and Pfizer; ClinicalTrials.gov number, NCT04816643.)

Use of pneumococcal conjugate vaccines (PCVs) has led to substantial reductions in the global burden of pediatric pneumococcal disease. Expansion of serotype coverage has been achieved by increasing PCV valency, but this may carry the potential risk of antibody interference. A complementary 7-valent PCV (cPCV7) including polysaccharide conjugates from 7 non-13-valent (PCV13) serotypes was developed to potentially complement PCV13-mediated protection and expand serotype coverage. This study evaluated cPCV7 and PCV13 coadministered in separate limbs or separated in time in infants. This phase 2, multicenter, open-label study included 512 infants randomized 1:1:1 to receive cPCV7 coadministered with PCV13 at ages 2, 4, 6, and 12 months (cPCV7 Coadministered); cPCV7 given at ages 3, 5, 7, and 13 months, 3-5 weeks after PCV13 (cPCV7 Separated); or PCV13 at ages 2, 4, 6, and 12 months followed by a single supplemental dose of cPCV7 at 13 months (PCV13 Control). Safety evaluations included local reactions, systemic events, and adverse events. Serotype-specific immunoglobulin G concentrations and opsonophagocytic activity titers were assessed. The safety profile of cPCV7 was similar to that of PCV13. cPCV7 was well-tolerated in infants when coadministered with or given separately from PCV13. Robust and functional immune responses for all cPCV7 serotypes were observed in both cPCV7 groups. No immunologic interference was observed for either the cPCV7 or PCV13 serotypes with coadministration. A single cPCV7 dose induced immune responses in toddlers. These findings support potential coadministration of a complementary PCV to supplement protection provided by existing PCVs.Trial registration: ClinicalTrials.gov, NCT03550313.

BACKGROUND:The emergence of immune-escape variants of severe acute respiratory syndrome coronavirus 2 warrants the use of sequence-adapted vaccines to provide protection against coronavirus disease 2019. METHODS:In an ongoing phase 3 trial, adults older than 55 years who had previously received three 30-μg doses of the BNT162b2 vaccine were randomly assigned to receive 30 μg or 60 μg of BNT162b2, 30 μg or 60 μg of monovalent B.1.1.529 (omicron) BA.1-adapted BNT162b2 (monovalent BA.1), or 30 μg (15 μg of BNT162b2 + 15 μg of monovalent BA.1) or 60 μg (30 μg of BNT162b2 + 30 μg of monovalent BA.1) of BA.1-adapted BNT162b2 (bivalent BA.1). Primary objectives were to determine superiority (with respect to 50% neutralizing titer [NT50] against BA.1) and noninferiority (with respect to seroresponse) of the BA.1-adapted vaccines to BNT162b2 (30 μg). A secondary objective was to determine noninferiority of bivalent BA.1 to BNT162b2 (30 μg) with respect to neutralizing activity against the ancestral strain. Exploratory analyses assessed immune responses against omicron BA.4, BA.5, and BA.2.75 subvariants. RESULTS:A total of 1846 participants underwent randomization. At 1 month after vaccination, bivalent BA.1 (30 μg and 60 μg) and monovalent BA.1 (60 μg) showed neutralizing activity against BA.1 superior to that of BNT162b2 (30 μg), with NT50 geometric mean ratios (GMRs) of 1.56 (95% confidence interval [CI], 1.17 to 2.08), 1.97 (95% CI, 1.45 to 2.68), and 3.15 (95% CI, 2.38 to 4.16), respectively. Bivalent BA.1 (both doses) and monovalent BA.1 (60 μg) were also noninferior to BNT162b2 (30 μg) with respect to seroresponse against BA.1; between-group differences ranged from 10.9 to 29.1 percentage points. Bivalent BA.1 (either dose) was noninferior to BNT162b2 (30 μg) with respect to neutralizing activity against the ancestral strain, with NT50 GMRs of 0.99 (95% CI, 0.82 to 1.20) and 1.30 (95% CI, 1.07 to 1.58), respectively. BA.4-BA.5 and BA.2.75 neutralizing titers were numerically higher with 30-μg bivalent BA.1 than with 30-μg BNT162b2. The safety profile of either dose of monovalent or bivalent BA.1 was similar to that of BNT162b2 (30 μg). Adverse events were more common in the 30-μg monovalent-BA.1 (8.5%) and 60-μg bivalent-BA.1 (10.4%) groups than in the other groups (3.6 to 6.6%). CONCLUSIONS:The candidate monovalent or bivalent omicron BA.1-adapted vaccines had a safety profile similar to that of BNT162b2 (30 μg), induced substantial neutralizing responses against ancestral and omicron BA.1 strains, and, to a lesser extent, neutralized BA.4, BA.5, and BA.2.75 strains. (Funded by BioNTech and Pfizer; ClinicalTrials.gov number, NCT04955626.).

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.).

What is this summary about? This is a summary of an article about part of a clinical study for the BNT162b2 COVID-19 vaccine, also called the Pfizer-BioNTech vaccine. The article was published in the New England Journal of Medicine in May 2021. This summary describes how the vaccine worked in participants 12- to 15-years old. The part of the study described in the article is ongoing and expected to finish March 2023. This means that the final results may be different from the results included in this summary. What happened in this study? The part of the study described in this summary included participants 12- to 15-years old who had no serious health issues. The BNT162b2 vaccine had already been studied in participants 16 years of age or older. In this part of the study, the researchers wanted to find out: How effective and safe the vaccine was in participants 12- to 15-years old. What the immune response to the vaccine and the vaccine safety were like in 12- to 15-year-olds compared with 16- to 25-year-olds. How well the vaccine prevented SARS-CoV-2 infections in participants who received the vaccine compared to those who did not. This is also called efficacy of the BNT162b2 vaccine Half of the participants in this study received 2 injections of the BNT162b2 vaccine and half received 2 injections of a placebo in a muscle of the upper arm. The placebo looked like the BNT162b2 vaccine but did not have any active vaccine in it. What were the results? BNT162b2 had a favorable safety profile. The most common reactions were pain at the injection site, fatigue, and headache. None of the participants had serious reactions to the vaccine. The 12- to 15-year-old participants' immune system responses to the BNT162b2 vaccine were as good as or stronger than the 16- to 25-year-old participants' immune responses. The participants who received the BNT162b2 vaccine were less likely to get COVID-19 compared with the participants who got the placebo. Clinical Trial Registration: NCT04368728 ( ClinicalTrials.gov )