Respiratory Syncytial Virus Prefusion F Vaccination: Antibody Persistence and Revaccination.

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. 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. 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. RSVpreF revaccination was immunogenic and well tolerated among adults. Clinical Trials Registration. NCT03529773 (ClinicalTrials.gov).

Walsh EE ，Falsey AR ，Zareba AM ，Jiang Q ，Gurtman A ，Radley D ，Gomme E ，Cooper D ，Jansen KU ，Gruber WC ，Swanson KA ，Schmoele-Thoma B ... -  《-》

Efficacy, Safety, and Immunogenicity of the MATISSE (Maternal Immunization Study for Safety and Efficacy) Maternal Respiratory Syncytial Virus Prefusion F Protein Vaccine Trial.

To evaluate descriptive efficacy data, exploratory immunogenicity data, and safety follow-up through study completion from the global, phase 3 MATISSE (Maternal Immunization Study for Safety and Efficacy) maternal vaccination trial of bivalent respiratory syncytial virus (RSV) prefusion F protein vaccine (RSVpreF). MATISSE was a phase 3, randomized, double-blinded, placebo-controlled trial. Healthy pregnant participants aged 49 years or younger at 24-36 weeks of gestation were randomized (1:1) to receive a single RSVpreF 120 micrograms or placebo dose. Primary efficacy endpoints included newborn and infant severe RSV-associated medically attended lower respiratory tract illness within 180 days after birth. The RSV-A and RSV-B serum neutralizing antibody titers were determined in a subset of pregnant participants and their newborns. In this final analysis, 7,420 pregnant participants were randomized, and 7,307 children were born (RSVpreF n=3,660, placebo n=3,647). Vaccine efficacy , defined as protection against newborn and infant severe RSV-associated medically attended lower respiratory tract illness, was 82.4% (95% CI, 57.5-93.9) and 70.0% (95% CI, 50.6-82.5) within 90 and 180 days of birth, respectively. The RSVpreF induced robust immune responses in pregnant participants and resulted in highly efficient transfer of maternal antibodies to their newborns across subgroups (by gestational age at delivery and at vaccination, number of days from vaccination to delivery, country, maternal age). Final RSVpreF safety results in pregnant and newborn and infant participants were consistent with the primary analysis with no new safety concerns identified. This final analysis of MATISSE trial data confirms the primary analysis conclusions: Maternal vaccination with RSVpreF has a favorable safety profile in both pregnant and newborn and infant participants and demonstrates efficacy against RSV-associated lower respiratory tract illness in infants through age 6 months. The RSVpreF induces robust immune responses in pregnant individuals, with corresponding high RSV-neutralizing titers in their newborns. ClinicalTrials.gov , NCT04424316.

Simões EAF ，Pahud BA ，Madhi SA ，Kampmann B ，Shittu E ，Radley D ，Llapur C ，Baker J ，Pérez Marc G ，Barnabas SL ，Fausett M ，Adam T ，Perreras N ，Van Houten MA ，Kantele A ，Huang LM ，Bont LJ ，Otsuki T ，Vargas SL ，Gullam J ，Tapiero B ，Stein RT ，Polack FP ，Zar HJ ，Staerke NB ，Padilla MD ，Richmond PC ，Sarwar UN ，Baber J ，Koury K ，Lino MM ，Kalinina EV ，Li W ，Cooper D ，Anderson AS ，Swanson KA ，Gurtman A ，Munjal I ，MATISSE (Maternal Immunization Study for Safety and Efficacy) Clinical Trial Group ... -  《-》

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

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. 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. 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. 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).

Schwarz TF ，Hwang SJ ，Ylisastigui P ，Liu CS ，Takazawa K ，Yono M ，Ervin JE ，Andrews CP ，Fogarty C ，Eckermann T ，Collete D ，de Heusch M ，De Schrevel N ，Salaun B ，Lambert A ，Maréchal C ，Olivier A ，Nakanwagi P ，Lievens M ，Hulstrøm V ... -  《-》

Safety and immunogenicity of the Ad26/protein preF RSV vaccine in adults aged 18 to 59 years with and without at-risk comorbidities for severe respiratory syncytial virus disease: A phase 3, randomized, controlled, immunobridging trial.

Respiratory syncytial virus (RSV) causes a significant disease burden in adults with chronic comorbidities. Rates of severe RSV disease and death are as high, or higher in younger adults with risk factors than in healthy older adults in whom RSV vaccination is recommended. We conducted an immunobridging study using the Ad26/protein RSV preF vaccine, which previously demonstrated efficacy in adults aged ≥65 years to support extrapolation of efficacy demonstrated in an older population to younger adult populations at high risk of severe RSV disease. This Phase 3 randomized, double-blind, placebo-controlled trial assessed the safety/tolerability and immunogenicity of Ad26/protein preF RSV in adults aged 18-59 years without (Cohort 1) and with (Cohort 2) chronic cardiac or pulmonary comorbidities, compared to adults aged ≥65 years (Cohort 3) in whom efficacy against RSV disease was demonstrated. Humoral and cellular immune responses were assessed at baseline, Days 15 and 183. Reactogenicity and safety were assessed in all participants. 1118 participants were enrolled (Cohort 1: 387; Cohort 2: 388; Cohort 3: 343). Compared to adults aged ≥65 years RSV neutralizing antibody titers were non-inferior in adults aged 18-59 years, including those at high risk. Levels of pre-F A IgG antibodies and frequencies of RSV-F specific interferon-gamma T-cells increased by Day 15 post-vaccination, and remained above baseline for at least 6 months in all cohorts. Reactogenicity and safety were clinically acceptable but age-dependent, with higher rates of Grade 3 systemic adverse events in adults aged 18-59-years than adults ≥65 years. Ad26/protein preF RSV vaccine induced robust humoral and cellular immune responses in adults aged 18-59 years with or without chronic cardiac or pulmonary comorbidities, of similar magnitude to responses in older adults, allowing inference of efficacy and protection against RSV-associated respiratory disease in this population. www. govNCT05070546.

Jastorff A ，Gymnopoulou E ，Salas J ，Merrall E ，Buntinx E ，Martin C ，Askling HH ，Schenkenberger I ，Yuste AC ，Smith W ，Sotolongo R ，Von Engelhardt C ，Bastian AR ，Comeaux C ，Ligtenberg N ，Callendret B ，Heijnen E ... -  《-》

Immunogenicity and safety of different dose levels of Ad26.RSV.preF/RSV preF protein vaccine in adults aged 60 years and older: A randomized, double-blind, placebo-controlled, phase 2a study.

van Heesbeen R ，Bastian AR ，Omoruyi E ，Rosen J ，Comeaux CA ，Callendret B ，Heijnen E ... -  《-》