Noninferior Immunogenicity and Consistent Safety of Respiratory Syncytial Virus Prefusion F Protein Vaccine in Adults 50–59 Years Compared to ≥60 Years of Age
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 ,   the RSV OA=ADJ-018 Study Group, Abd-Elaziz Khalid S , Adams Mark S , Barts Agnieszka , Cannon Kevin , Davis Matthew , de las Fuentes Galán Sonia , de los Ríos Rodríguez Marta , De Salvo Maria Cristina , DeGregoria Lauren , del Campo Pérez Víctor , Drescher Torsten , Dunsmoor-Su Rebecca , Dzongowski Peter , Echave-Sustaeta Jose Ma , Eckermann Tamara Julia , Fuller Ashley E , Garí Parera Jaume , Gauthier Jean Sebastien , Geller Steven , Ghesquiere Wayne , Gonzalez Antonio , González Cediel Patricia , Grasch Anton , Helman Laura L , Hernandez Susan , Herranz Urbasos María , Itcovici Nicolas , Klein Terry , Labrador Gómez Jorge , Blanco Antonio Lalueza , Leblanc Ryan , Luttermann Matthias , Marks Kristen , Masuet-Aumatell Cristina , Möckesch Leonie , Michelle Moreno Silva Tamara , Narejos Perez Silvia , Noveck Robert J , Oude Nijhuis Jérôme C , Paquette Jean-Sebastien , Pek Bonavuth , Plassmann Georg , Pritt Robert , Palma Mireia Puig , Rocha-Calderon Claudio , Royer Paule , Shu David , Sia Ying Tung , Sieber Angelika , Simmons Todd , Sinclair Leslie , Smith William B , Soufer Joseph , Suarez Simón Ana , Rifa Genoveva Vilardell , Teresa Vilella Moreno María , Weber Ulrich , de la Higuera Alba María Yañez , Ylisastigui Pedro 
Published: August 2024

Abstract

Background
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.

Methods
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.

Results
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.

Conclusions
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.

Clinical Trial Registration
ClinicalTrials.gov: NCT05590403.