Immunogenicity and Safety Following 1 Dose of AS01E-Adjuvanted Respiratory Syncytial Virus Prefusion F Protein Vaccine in Older Adults: A Phase 3 Trial.

BACKGROUND: The recently approved AS01E-adjuvanted respiratory syncytial virus (RSV) prefusion F protein-based vaccine for older adults (RSVPreF3 OA) demonstrated high efficacy against RSV-related disease in ≥60-year-olds. METHODS: This ongoing phase 3 study in ≥60-year-olds evaluates immune persistence until 3 years after RSVPreF3 OA vaccination. Here, we describe interim results on humoral and cell-mediated immunogenicity, reactogenicity, and safety until 1 year post-dose 1. RESULTS: In total, 1653 participants were vaccinated. One month post-dose 1, neutralization titers increased 10.5-fold (RSV-A) and 7.8-fold (RSV-B) vs pre-dose 1. Titers then declined to levels 4.4-fold (RSV-A) and 3.5-fold (RSV-B) above pre-dose 1 at month 6 and remained 3.1-fold (RSV-A) and 2.3-fold (RSV-B) above pre-dose 1 levels after 1 year. RSVPreF3-binding immunoglobulin G levels and CD4+ T-cell frequencies showed similar kinetics. Solicited administration-site and systemic adverse events (mostly mild to moderate and transient) were reported by 62.2% and 49.5% of participants. Serious adverse events were reported by 3.9% of participants within 6 months post-dose 1; 1 case was considered vaccine related. CONCLUSIONS: One RSVPreF3 OA dose elicited cell-mediated and RSV-A- and RSV-B-specific humoral immune responses that declined over time but remained above pre-dose 1 levels for at least 1 year. The vaccine was well tolerated with an acceptable safety profile. Clinical Trials Registration. NCT04732871 (ClinicalTrials.gov).

Respiratory syncytial virus (RSV) is a major cause of illness and hospitalization in older adults. An RSV vaccine for older adults developed by GSK was recently approved. The vaccine was well tolerated and provided protection against RSV disease in adults aged ≥60 years during at least 1 RSV season. In this ongoing study, we are evaluating the magnitude and durability of the immune response, as well as vaccine safety, until 3 years after vaccination of adults aged ≥60 years from 5 countries. Here, we report the results of an interim analysis until 1 year after vaccination with 1 dose. In total, 1653 participants were vaccinated. We found that the vaccine induced a strong immune response that was evident 1 month after vaccination, after which it declined but persisted for at least 1 year. Study participants most often reported pain at the injection site, muscle pain, tiredness, and headache as adverse reactions, which were mostly mild to moderate and of short duration. One serious adverse reaction was considered related to the vaccine. The long-term immune response that was observed in this study is consistent with the vaccine providing protection during at least 1 RSV season.

Nonadjuvanted Bivalent Respiratory Syncytial Virus Vaccination and Perinatal Outcomes.

Importance: A nonadjuvanted bivalent respiratory syncytial virus (RSV) prefusion F (RSVpreF [Pfizer]) protein subunit vaccine was newly approved and recommended for pregnant individuals at 32 0/7 to 36 6/7 weeks' gestation during the 2023 to 2024 RSV season; however, clinical vaccine data are lacking. Objective: To evaluate the association between prenatal RSV vaccination status and perinatal outcomes among patients who delivered during the vaccination season. Design, Setting, and Participants: This retrospective observational cohort study was conducted at 2 New York City hospitals within 1 health care system among patients who gave birth to singleton gestations at 32 weeks' gestation or later from September 22, 2023, to January 31, 2024. Exposure: Prenatal RSV vaccination with the RSVpreF vaccine captured from the health system's electronic health records. Main Outcome and Measures: The primary outcome is preterm birth (PTB), defined as less than 37 weeks' gestation. Secondary outcomes included hypertensive disorders of pregnancy (HDP), stillbirth, small-for-gestational age birth weight, neonatal intensive care unit (NICU) admission, neonatal respiratory distress with NICU admission, neonatal jaundice or hyperbilirubinemia, neonatal hypoglycemia, and neonatal sepsis. Logistic regression models were used to estimate odds ratios (ORs), and multivariable logistic regression models and time-dependent covariate Cox regression models were performed. Results: Of 2973 pregnant individuals (median [IQR] age, 34.9 [32.4-37.7] years), 1026 (34.5%) received prenatal RSVpreF vaccination. Fifteen patients inappropriately received the vaccine at 37 weeks' gestation or later and were included in the nonvaccinated group. During the study period, 60 patients who had evidence of prenatal vaccination (5.9%) experienced PTB vs 131 of those who did not (6.7%). Prenatal vaccination was not associated with an increased risk for PTB after adjusting for potential confounders (adjusted OR, 0.87; 95% CI, 0.62-1.20) and addressing immortal time bias (hazard ratio [HR], 0.93; 95% CI, 0.64-1.34). There were no significant differences in pregnancy and neonatal outcomes based on vaccination status in the logistic regression models, but an increased risk of HDP in the time-dependent model was seen (HR, 1.43; 95% CI, 1.16-1.77). Conclusions and Relevance: In this cohort study of pregnant individuals who delivered at 32 weeks' gestation or later, the RSVpreF vaccine was not associated with an increased risk of PTB and perinatal outcomes. These data support the safety of prenatal RSVpreF vaccination, but further investigation into the risk of HDP is warranted.

A Randomized, Double-Blind, Placebo-Controlled, Phase 1 Study to Evaluate the Safety, Reactogenicity, and Immunogenicity of Single Vaccination of Ad26.RSV.preF-Based Regimen in Japanese Adults Aged 60 Years and Older.

BACKGROUND: Respiratory syncytial virus (RSV) is increasingly recognized as a significant cause of lower respiratory tract disease (LRTD) in older adults. The Ad26.RSV.preF/RSV preF protein vaccine demonstrated protective efficacy against RSV related LRTD in a Phase 2b study in the United States. Hence, Ad26.RSV.preF/RSV preF protein vaccine candidate was evaluated in the Japanese older adult population. METHODS: This Phase 1 study evaluated safety, reactogenicity, and immunogenicity of Ad26.RSV.preF/RSV preF protein vaccine at dose level of 1 × 1011 vp/150 µg in Japanese healthy adult aged ≥60 years. The study included a screening Phase, vaccination, 28-day follow up Phase, a 182-day follow-up period, and final visit on Day 183. A total of 36 participants were randomized in a 2:1 ratio to receive Ad26.RSV.preF/RSV preF protein vaccine (n = 24) or placebo (n = 12). After study intervention administration, the safety and immunogenicity analysis were performed as per planned schedule. Immune responses including virus-neutralizing and preF-specific binding antibodies were measured on Days 1, 15, 29, and 183. RESULTS: There were no deaths, SAEs, or AEs leading to discontinuation reported during the study. The Ad26.RSV.preF/RSV preF protein vaccine had acceptable safety and tolerability profile with no safety concern in Japanese older adults. The Ad26.RSV.preF/RSV preF protein vaccine induced RSV-specific humoral immunity, with increase in antibody titers on Days 15 and 29 compared with baseline which was well maintained until Day 183. CONCLUSIONS: A single dose of Ad26.RSV.preF/RSV preF protein vaccine had an acceptable safety and tolerability profile and induced RSV-specific humoral immunity in Japanese healthy adults. TRIAL REGISTRATION: NCT number: NCT04354480; Clinical Registry number: CR108768.

Exacerbated lung inflammation in offspring with high maternal antibody levels following secondary RSV exposure.

Respiratory syncytial virus (RSV) is the primary cause of bronchiolitis-related hospitalizations among children under 5 years of age, with reinfection being common throughout life. Maternal vaccination has emerged as a promising strategy, delivering elevated antibody levels to newborns for immediate protection. However, limited research has explored the protective efficacy of maternal antibodies (matAbs) against secondary RSV infections in offspring. To address this gap, we employed a mouse model of maternal RSV vaccination and secondary infection of offspring to evaluate lung pathology following RSV reinfection in mice with varying levels of maternal antibody (matAb). Additionally, we aimed to investigate the potential causes of exacerbated lung inflammation in offspring with high matAb levels following secondary RSV exposure. Our findings revealed that offspring with elevated levels of maternal pre-F antibody demonstrated effective protection against lung pathology following the initial RSV infection. However, this protection was compromised upon reinfection, manifesting as heightened weight loss, exacerbated lung pathology, increased expression of RSV-A N genes, eosinophilia, enhanced IL-5, IL-13, MUC5AC, and eosinophils Major Basic Protein (MBP) production in lung tissue compared to offspring lacking matAbs. Importantly, these unexpected outcomes were not attributed to antibody-dependent enhancement (ADE) resulting from declining matAb levels over time. Notably, our findings showed a decline in secretory IgA (sIgA), mucosal IgA, and mucosal IgG levels in offspring with high matAb levels post-primary RSV challenge. We propose that this decline may be a critical factor contributing to the ineffective protection observed during secondary RSV exposure. Overall, these findings offer valuable insights into maternal vaccination against RSV, contributing to a comprehensive understanding and mitigation of potential risks associated with maternal RSV vaccination.

Immunogenicity and safety of Ad26.RSV.preF/RSV preF protein vaccine at predicted intermediate- and end-of-shelf-life as an evaluation of potency throughout shelf life.

This study assessed three Ad26.RSV.preF/RSV preF protein combinations, combining different Ad26.RSV.preF doses and naturally aged preF protein, representing the expected critical vaccine quality attributes close to release, around intermediate shelf-life (ISL) and near-presumed end-of-shelf-life (EoSL), as a way to evaluate the vaccine immunogenicity and safety throughout its shelf-life. A single dose of Ad26.RSV.preF/RSV preF protein vaccine was administered to adults 60-75 years of age. Solicited adverse events (AEs), unsolicited AEs, and serious AEs (SAEs) were assessed for 7-day, 28-day, and 6-month periods after vaccination, respectively. RSV preF-binding antibody concentrations and RSV neutralizing titers were measured 14 days post-vaccination as primary and secondary endpoints, respectively; binding antibodies were also measured 6 months post-vaccination. The RSV preF-binding antibody responses induced by Ad26.RSV.preF/RSV preF protein vaccine lots representing the critical quality attributes around ISL and near presumed EoSL were noninferior to the responses induced by the vaccine lot representing the critical quality attributes near release. The RSV preF-binding and RSV neutralizing antibody levels measured 14 days post-vaccination were similar across the 3 groups. RSV preF-binding antibody concentrations were also similar 6 months post-vaccination. Solicited AEs were mostly mild to moderate in intensity, and a decreased reactogenicity was observed from the Release group to the ISL and EoSL group. None of the reported SAEs were considered related to study vaccination. The study provided evidence of sustained immunogenicity and safety over the intended shelf-life of the Ad26.RSV.pref/RSV preF protein vaccine. The three vaccine lots had acceptable safety profiles.

Exploring parental perspectives: Maternal RSV vaccination versus infant RSV monoclonal antibody.

Respiratory Syncytial Virus poses a significant global public health threat, particularly affecting infants aged less than one year of age. Recently, two forms of passive immunization against infant RSV have been developed and brought to market; nirsevimab a long-acting monoclonal antibody (mAb) and RSV-PreF, a maternal RSV vaccine. The acceptability and uptake of these products will play a pivotal role in determining the success of any national immunization strategy aimed at safeguarding infants from RSV. It is crucial at this time to reflect on the factors that influence parental decisions surrounding immunization to facilitate more informed discussions, enhance healthcare communication, and contribute to the design of effective RSV prevention strategies that resonate with the concerns and aspirations of parents worldwide.

Respiratory syncytial virus vaccination during pregnancy for improving infant outcomes.

BACKGROUND: Respiratory syncytial virus (RSV) is a major cause of lower respiratory tract infections (LRTIs) in infants. Maternal RSV vaccination is a preventive strategy of great interest, as it could have a substantial impact on infant RSV disease burden. In recent years, the clinical development of maternal RSV vaccines has advanced rapidly. OBJECTIVES: To assess the efficacy and safety of maternal respiratory syncytial virus (RSV) vaccination for preventing RSV disease in infants. SEARCH METHODS: We searched Cochrane Pregnancy and Childbirth's Trials Register and two other trials registries on 21 October 2022. We updated the search on 27 July 2023, when we searched MEDLINE, Embase, CENTRAL, CINAHL, and two trials registries. Additionally, we searched the reference lists of retrieved studies and conference proceedings. There were no language restrictions on our searches. SELECTION CRITERIA: We included randomised controlled trials (RCTs) comparing maternal RSV vaccination with placebo or no intervention in pregnant women of any age. The primary outcomes were hospitalisation with clinically confirmed or laboratory-confirmed RSV disease in infants. The secondary outcomes covered adverse pregnancy outcomes (intrauterine growth restriction, stillbirth, and maternal death) and adverse infant outcomes (preterm birth, congenital abnormalities, and infant death). DATA COLLECTION AND ANALYSIS: We used standard Cochrane methods and assessed the certainty of evidence using the GRADE approach. MAIN RESULTS: We included six RCTs (25 study reports) involving 17,991 pregnant women. The intervention was an RSV pre-F protein vaccine in four studies, and an RSV F protein nanoparticle vaccine in two studies. In all studies, the comparator was a placebo (saline, formulation buffer, or sterile water). We judged four studies at overall low risk of bias and two studies at overall high risk (mainly due to selection bias). All studies were funded by pharmaceutical companies. Maternal RSV vaccination compared with placebo reduces infant hospitalisation with laboratory-confirmed RSV disease (risk ratio (RR) 0.50, 95% confidence interval (CI) 0.31 to 0.82; 4 RCTs, 12,216 infants; high-certainty evidence). Based on an absolute risk with placebo of 22 hospitalisations per 1000 infants, our results represent 11 fewer hospitalisations per 1000 infants from vaccinated pregnant women (15 fewer to 4 fewer). No studies reported infant hospitalisation with clinically confirmed RSV disease. Maternal RSV vaccination compared with placebo has little or no effect on the risk of congenital abnormalities (RR 0.96, 95% CI 0.88 to 1.04; 140 per 1000 with placebo, 5 fewer per 1000 with RSV vaccination (17 fewer to 6 more); 4 RCTs, 12,304 infants; high-certainty evidence). Maternal RSV vaccination likely has little or no effect on the risk of intrauterine growth restriction (RR 1.32, 95% CI 0.75 to 2.33; 3 per 1000 with placebo, 1 more per 1000 with RSV vaccination (1 fewer to 4 more); 4 RCTs, 12,545 pregnant women; moderate-certainty evidence). Maternal RSV vaccination may have little or no effect on the risk of stillbirth (RR 0.81, 95% CI 0.38 to 1.72; 3 per 1000 with placebo, no difference with RSV vaccination (2 fewer to 3 more); 5 RCTs, 12,652 pregnant women). There may be a safety signal warranting further investigation related to preterm birth. This outcome may be more likely with maternal RSV vaccination, although the 95% CI includes no effect, and the evidence is very uncertain (RR 1.16, 95% CI 0.99 to 1.36; 6 RCTs, 17,560 infants; very low-certainty evidence). Based on an absolute risk of 51 preterm births per 1000 infants from pregnant women who received placebo, there may be 8 more per 1000 infants from pregnant women with RSV vaccination (1 fewer to 18 more). There was one maternal death in the RSV vaccination group and none in the placebo group. Our meta-analysis suggests that RSV vaccination compared with placebo may have little or no effect on the risk of maternal death (RR 3.00, 95% CI 0.12 to 73.50; 3 RCTs, 7977 pregnant women; low-certainty evidence). The effect of maternal RSV vaccination on the risk of infant death is very uncertain (RR 0.81, 95% CI 0.36 to 1.81; 6 RCTs, 17,589 infants; very low-certainty evidence). AUTHORS' CONCLUSIONS: The findings of this review suggest that maternal RSV vaccination reduces laboratory-confirmed RSV hospitalisations in infants. There are no safety concerns about intrauterine growth restriction and congenital abnormalities. We must be careful in drawing conclusions about other safety outcomes owing to the low and very low certainty of the evidence. The evidence available to date suggests RSV vaccination may have little or no effect on stillbirth, maternal death, and infant death (although the evidence for infant death is very uncertain). However, there may be a safety signal warranting further investigation related to preterm birth. This is driven by data from one trial, which is not fully published yet. The evidence base would be much improved by more RCTs with substantial sample sizes and well-designed observational studies with long-term follow-up for assessment of safety outcomes. Future studies should aim to use standard outcome measures, collect data on concomitant vaccines, and stratify data by timing of vaccination, gestational age at birth, race, and geographical setting.

Equivalent immunogenicity across three RSVpreF vaccine lots in healthy adults 18-49 years of age: Results of a randomized phase 3 study.

BACKGROUND: Bivalent RSV prefusion F subunit vaccine (RSVpreF), comprised of equal quantities of stabilized prefusion F antigens from the major circulating subgroups (RSV A, RSV B), is licensed for prevention of RSV-associated lower respiratory tract illness (LRTI) in older adults and for maternal vaccination for prevention of RSV-associated LRTI in infants. To support licensure and large-scale manufacturing, this lot consistency study was conducted to demonstrate equivalence in immunogenicity across 3 RSVpreF lots. METHODS: This phase 3, multicenter, parallel-group, placebo-controlled, randomized (1:1:1:1), double-blind study evaluated immunogenicity, safety, and tolerability of RSVpreF in healthy 18-49-year-old adults. Participants received a single 120-µg injection of 1 of 3RSVpreF lots or placebo. Geometric mean ratio (GMR) of RSV serum 50 % neutralizing geometric mean titers obtained 1 month after vaccination were compared between each vaccine lot for RSV A and RSV B, separately. Equivalence between lots was defined using a 1.5-fold criterion (GMR 95 % CIs for every lot pair within the 0.667-1.5 interval). Safety and tolerability were assessed. RESULTS: Of 992participants vaccinated, 948 were included in the evaluable immunogenicity population. All 3 RSVpreF lots elicited strong immune responses, meeting the 1.5-fold equivalence criterion for all between-lot comparisons for both RSV A and RSV B. Across the 3 lots, RSV A and RSV B 50 % neutralizing geometric mean titers substantially increased from baseline (RSV A, 1671-1795; RSV B 1358-1429) to 1 month after RSVpreF vaccination (RSV A, 24,131-25,238; RSV B, 19,238-21,702), corresponding to ≥14-fold increases in 50 % neutralizing titers for both RSV A and RSV B from before to 1 month after vaccination. Single doses of RSVpreF were safe and well tolerated, with similar safety profiles across the 3 RSVpreF lots. CONCLUSIONS: These findings support the reproducibility of RSVpreF vaccine manufacturing with similar safety and reactogenicity profiles (NCT05096208).

RSV Prefusion F Protein-Based Maternal Vaccine - Preterm Birth and Other Outcomes.

BACKGROUND: Vaccination against respiratory syncytial virus (RSV) during pregnancy may protect infants from RSV disease. Efficacy and safety data on a candidate RSV prefusion F protein-based maternal vaccine (RSVPreF3-Mat) are needed. METHODS: We conducted a phase 3 trial involving pregnant women 18 to 49 years of age to assess the efficacy and safety of RSVPreF3-Mat. The women were randomly assigned in a 2:1 ratio to receive RSVPreF3-Mat or placebo between 24 weeks 0 days and 34 weeks 0 days of gestation. The primary outcomes were any or severe medically assessed RSV-associated lower respiratory tract disease in infants from birth to 6 months of age and safety in infants from birth to 12 months of age. After the observation of a higher risk of preterm birth in the vaccine group than in the placebo group, enrollment and vaccination were stopped early, and exploratory analyses of the safety signal of preterm birth were performed. RESULTS: The analyses included 5328 pregnant women and 5233 infants; the target enrollment of approximately 10,000 pregnant women and their infants was not reached because enrollment was stopped early. A total of 3426 infants in the vaccine group and 1711 infants in the placebo group were followed from birth to 6 months of age; 16 and 24 infants, respectively, had any medically assessed RSV-associated lower respiratory tract disease (vaccine efficacy, 65.5%; 95% credible interval, 37.5 to 82.0), and 8 and 14, respectively, had severe medically assessed RSV-associated lower respiratory tract disease (vaccine efficacy, 69.0%; 95% credible interval, 33.0 to 87.6). Preterm birth occurred in 6.8% of the infants (237 of 3494) in the vaccine group and in 4.9% of those (86 of 1739) in the placebo group (relative risk, 1.37; 95% confidence interval [CI], 1.08 to 1.74; P = 0.01); neonatal death occurred in 0.4% (13 of 3494) and 0.2% (3 of 1739), respectively (relative risk, 2.16; 95% CI, 0.62 to 7.56; P = 0.23), an imbalance probably attributable to the greater percentage of preterm births in the vaccine group. No other safety signal was observed. CONCLUSIONS: The results of this trial, in which enrollment was stopped early because of safety concerns, suggest that the risks of any and severe medically assessed RSV-associated lower respiratory tract disease among infants were lower with the candidate maternal RSV vaccine than with placebo but that the risk of preterm birth was higher with the candidate vaccine. (Funded by GlaxoSmithKline Biologicals; ClinicalTrials.gov number, NCT04605159.).

Arexvy: A Comprehensive Review of the Respiratory Syncytial Virus Vaccine for Revolutionary Protection.

The respiratory syncytial virus (RSV) is a major cause of acute lower respiratory tract infection in children and poses a significant risk to older adults. Developing a vaccine against RSV has been a priority, and the recently approved Arexvy vaccine has shown promise in preventing lower respiratory tract disease (LRTD) caused by RSV in individuals aged 60 years and older. This comprehensive review discusses the history of RSV, challenges in vaccine development, and the mechanism of action of Arexvy. The efficacy and safety of the vaccine are explored based on phase 3 clinical trial, demonstrating its effectiveness in preventing RSV-associated LRTD. The most common adverse reactions reported include injection site pain, fatigue, myalgia, headache, and arthralgia. Ongoing research focuses on the long-term effectiveness of Arexvy, including the need for booster doses and its impact on reducing RSV-associated hospitalizations. The potential of Arexvy to lessen the burden of RSV-related illnesses, particularly in vulnerable populations, is highlighted, emphasizing the importance of widespread immunization efforts and accessibility to this groundbreaking vaccine.

Administration of the GSK Respiratory Syncytial Virus Vaccine to Pregnant Persons in Error.

The GSK and Pfizer respiratory syncytial virus (RSV) vaccines are both indicated for adults aged 60 years and older, but only the Pfizer product is approved for use in pregnancy to prevent RSV-associated lower respiratory tract disease in infants aged younger than 6 months. To assess for vaccine administration errors (ie, administration of the GSK RSV vaccine to pregnant persons) VAERS (Vaccine Adverse Event Reporting System), a U.S. passive reporting system, was searched for the time period from August 2023 to January 2024. A total of 113 reports of these administration errors were identified. Most reports (103, 91.2%) did not describe an adverse event. These administration errors are preventable with proper education and training and other preventive measures.

Efficacy and Safety of Respiratory Syncytial Virus (RSV) Prefusion F Protein Vaccine (RSVPreF3 OA) in Older Adults Over 2 RSV Seasons.

BACKGROUND: The adjuvanted RSV prefusion F protein-based vaccine (RSVPreF3 OA) was efficacious against RSV-related lower respiratory tract disease (RSV-LRTD) in ≥60-years-olds over 1 RSV season. We evaluated efficacy and safety of 1 RSVPreF3 OA dose and of 2 RSVPreF3 OA doses given 1 year apart against RSV-LRTD over 2 RSV seasons post-dose 1. METHODS: In this phase 3, blinded trial, ≥60-year-olds were randomized (1:1) to receive RSVPreF3 OA or placebo pre-season 1. RSVPreF3 OA recipients were re-randomized (1:1) to receive a second RSVPreF3 OA dose (RSV_revaccination group) or placebo (RSV_1dose group) pre-season 2; participants who received placebo pre-season 1 received placebo pre-season 2 (placebo group). Efficacy of both vaccine regimens against RSV-LRTD was evaluated over 2 seasons combined (confirmatory secondary objective, success criterion: lower limits of 2-sided CIs around efficacy estimates >20%). RESULTS: The efficacy analysis comprised 24 967 participants (RSV_1dose: 6227; RSV_revaccination: 6242; placebo: 12 498). Median efficacy follow-up was 17.8 months. Efficacy over 2 seasons of 1 RSVPreF3 OA dose was 67.2% (97.5% CI: 48.2-80.0%) against RSV-LRTD and 78.8% (95% CI: 52.6-92.0%) against severe RSV-LRTD. Efficacy over 2 seasons of a first dose followed by revaccination was 67.1% (97.5% CI: 48.1-80.0%) against RSV-LRTD and 78.8% (95% CI: 52.5-92.0%) against severe RSV-LRTD. Reactogenicity/safety of the revaccination dose were similar to dose 1. CONCLUSIONS: One RSVPreF3 OA dose was efficacious against RSV-LRTD over 2 RSV seasons in ≥60-year-olds. Revaccination 1 year post-dose 1 was well tolerated but did not seem to provide additional efficacy benefit in the overall study population. CLINICAL TRIALS REGISTRATION: ClinicalTrials.gov: NCT04886596.

Respiratory Syncytial Virus Maternal Vaccination in Infants below 6 Months of Age: Meta-Analysis of Safety, Immunogenicity, and Efficacy.

INTRODUCTION: Severe respiratory syncytial virus (RSV) disease is most prevalent during infancy, particularly in those born prematurely, who benefit least from maternal antibody transfers. Maternal immunization is an attractive prevention leading to vaccine clinical trials. This meta-analysis aimed to evaluate recent maternal RSV vaccine trials. METHODS: Following PRISMA-P guidelines for systematic reviews and registered at https://www.crd.york.ac.uk/prospero, this study shortlisted six randomized clinical trials of suitable quality from four databases. Meta-analysis evaluated vaccine safety, immunogenicity, and efficacy in infants and their mothers. RESULTS: From random-effects and fixed-effects meta-analysis between trial and control arms, the maternal post-vaccination geometric antibody (Ab) titers showed pooled standard mean differences (SMDs [95% CI]) at delivery of (4.14 [2.91-5.37]), (3.95 [2.79-5.11]), and (12.20 [7.76, 16.64]) for RSV neutralizing Ab A, B, and F IgG, respectively. Vaccine administration was more likely than placebo to cause local pain, erythema, swelling, and systemic myalgia. Furthermore, the Ab levels in infants at birth showed pooled SMDs of each RSV A (3.9 [2.81-4.99]), RSV B (1.86 [1.09-2.62]), and RSV F IgG (2.24 [1.24-3.23]). The overall reduction of RSV-related lower respiratory tract infections and hospitalizations in the first 6 months of life was 52% and 48%, respectively. CONCLUSIONS: Not only does antenatal RSV vaccination look safe and immunogenic in vaccinated mothers, but it also reliably provides effective antibody levels in infants and diminishes RSV-related severe disease in infants under 6 months of age.

Respiratory Syncytial Virus Prefusion F Protein Vaccine Is Efficacious in Older Adults With Underlying Medical Conditions.

BACKGROUND: Older adults with chronic cardiorespiratory or endocrine/metabolic conditions are at increased risk of respiratory syncytial virus (RSV)-related acute respiratory illness (RSV-ARI) and severe respiratory disease. In an ongoing, randomized, placebo-controlled, multicountry, phase 3 trial in ≥60-year-old participants, an AS01E-adjuvanted RSV prefusion F protein-based vaccine (RSVPreF3 OA) was efficacious against RSV-related lower respiratory tract disease (RSV-LRTD), severe RSV-LRTD, and RSV-ARI. We evaluated efficacy and immunogenicity among participants with coexisting cardiorespiratory or endocrine/metabolic conditions that increase the risk of severe RSV disease ("conditions of interest"). METHODS: Medically stable ≥60-year-old participants received 1 dose of RSVPreF3 OA or placebo. Efficacy against first RSV-LRTD and RSV-ARI episodes was assessed in subgroups with/without coexisting cardiorespiratory or endocrine/metabolic conditions of interest. Immunogenicity was analyzed post hoc in these subgroups. RESULTS: In total, 12 467 participants received RSVPreF3 OA and 12 499 received placebo. Of these, 39.6% (RSVPreF3 OA) and 38.9% (placebo) had ≥1 coexisting condition of interest. The median efficacy follow-up was 6.7 months. Efficacy against RSV-LRTD was high in participants with ≥1 condition of interest (94.6%), ≥1 cardiorespiratory (92.1%), ≥1 endocrine/metabolic (100%), and ≥2 conditions of interest (92.0%). Efficacy against RSV-ARI was 81.0% in participants with ≥1 condition of interest (88.1% for cardiorespiratory, 79.4% for endocrine/metabolic conditions) and 88.0% in participants with ≥2 conditions of interest. Postvaccination neutralizing titers were at least as high in participants with ≥1 condition of interest as in those without. CONCLUSIONS: RSVPreF3 OA was efficacious against RSV-LRTD and RSV-ARI in older adults with coexisting medical conditions associated with an increased risk of severe RSV disease. CLINICAL TRIALS REGISTRATION: ClinicalTrials.gov: NCT04886596.

RSV vaccination strategies for high-risk patients 2023: a collaborative position paper by leading German medical societies and organizations.

Respiratory syncytial virus (RSV) inflicts severe illness and courses of infections not only in neonates, infants, and young children, but also causes significant morbidity and mortality in older adults and in people with immunosuppression, hemato-oncologic disease, chronic lung disease, or cardiovascular disease. In June and August 2023, effective vaccines against RSV were approved for the first time by the European Medicines Agency (EMA) for the EU. The respective pivotal studies showed a very high efficacy of the vaccine in preventing severe RSV-associated respiratory infections. At this point, use of the respective vaccines is restricted to persons aged 60 years or older, according to the registration studies. We therefore recommend use of the vaccination in persons aged 60 years or older. In addition, we recommend use of the vaccination in adults of any age with severe pulmonary or cardiovascular pre-existing conditions, as well as in adults with significant immune compromise, after individual consultation with the treating physician. Cost coverage can be applied for individually with the responsible health insurance company.