Noninferior Immunogenicity and Consistent Safety of Respiratory Syncytial Virus Prefusion F Protein Vaccine in Adults 50-59 Years Compared to ≥60 Years of Age

• Published in: Clinical infectious diseases Vol. 79; no. 4; p. 1074
• Main Authors: Ferguson, Murdo, Schwarz, Tino F, Núñez, Sebastián A, Rodríguez-García, Juan, Mital, Marek, Zala, Carlos, Schmitt, Bernhard, Toursarkissian, Nicole, Mazarro, Dolores Ochoa, Großkopf, Josef, Voors-Pette, Christine, Mehta, Hemalini, Hailemariam, Hiwot Amare, de Heusch, Magali, Salaun, Bruno, Damaso, Silvia, David, Marie-Pierre, Descamps, Dominique, Hill, Judith, Vandermeulen, Corinne, Hulstrøm, Veronica
• Format: Journal Article
• Language: English
• Published: United States 05.08.2024
• Subjects: Age Factors; Aged; Antibodies, Neutralizing - blood; Antibodies, Viral - blood; Female; Humans; Immunity, Cellular; Immunogenicity, Vaccine; Male; Middle Aged; Respiratory Syncytial Virus Infections - immunology; Respiratory Syncytial Virus Infections - prevention & control; Respiratory Syncytial Virus Vaccines - administration & dosage; Respiratory Syncytial Virus Vaccines - adverse effects; Respiratory Syncytial Virus Vaccines - immunology; Respiratory Syncytial Virus, Human - immunology; Vaccination; Viral Fusion Proteins - immunology; humoral immunity; respiratory syncytial virus; safety; chronic conditions; vaccination
• ISSN: 1537-6591
• DOI: 10.1093/cid/ciae364

The adjuvanted respiratory syncytial virus (RSV) prefusion F protein-based vaccine (RSVPreF3 OA) is approved in adults aged ≥60 years. We evaluated RSVPreF3 OA immunogenicity and safety in adults aged 50-59 years without or with increased risk for RSV disease due to specific chronic medical conditions. This observer-blind, phase 3, noninferiority trial included adults aged 50-59 years, stratified into 2 subcohorts: those with and those without predefined, stable, chronic medical conditions leading to an increased risk for RSV disease. Participants in both subcohorts were randomized 2:1 to receive RSVPreF3 OA or placebo. A control group of adults aged ≥60 years received RSVPreF3 OA. Primary outcomes were RSV-A and RSV-B neutralization titers (geometric mean titer ratios and sero-response rate differences) 1 month post-vaccination in 50-59-year-olds versus ≥60-year-olds. Cell-mediated immunity and safety were also assessed. The exposed population included 1152 participants aged 50-59 years and 381 participants aged ≥60 years. RSVPreF3 OA was immunologically noninferior in 50-59-year-olds versus ≥60-year-olds; noninferiority criteria were met for RSV-A and RSV-B neutralization titers in those with and those without increased risk for RSV disease. Frequencies of RSVPreF3-specific polyfunctional CD4+ T cells increased substantially from pre- to 1 month post-vaccination. Most solicited adverse events had mild-to-moderate intensity and were transient. Unsolicited and serious adverse event rates were similar in all groups. RSVPreF3 OA was immunologically noninferior in 50-59-year-olds compared to ≥60-year-olds, in whom efficacy was previously demonstrated. The safety profile in 50-59-year-olds was consistent with that in ≥60-year-olds. ClinicalTrials.gov: NCT05590403.