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

Author:

Ferguson Murdo1,Schwarz Tino F2,Núñez Sebastián A3,Rodríguez-García Juan4,Mital Marek5,Zala Carlos6,Schmitt Bernhard7,Toursarkissian Nicole8,Mazarro Dolores Ochoa9,Großkopf Josef10,Voors-Pette Christine11,Mehta Hemalini12,Hailemariam Hiwot Amare13,de Heusch Magali13,Salaun Bruno13,Damaso Silvia13,David Marie-Pierre13,Descamps Dominique13,Hill Judith13,Vandermeulen Corinne13ORCID,Hulstrøm Veronica13, ,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

Affiliation:

1. Colchester Research Group , Truro , Canada

2. Institute of Laboratory Medicine and Vaccination Centre, Klinikum Würzburg Mitte , Campus Juliusspital, Würzburg Mitte, Würzburg , Germany

3. Infectología, Centro Medico Maffei , Buenos Aires , Argentina

4. Preventive Medicine Department, Immunocompromised Patient Immunization Unit, Son Espases University Hospital, Palma de Mallorca , Mallorca, Balearic Islands , Spain

5. Agnieszka Mital Centrum Badan Clinic , Elblag , Poland

6. Vacunar, Sede Las Cañitas , Buenos Aires , Argentina

7. Studienzentrum Mainz Mitte , Mainz , Germany

8. Praxis Dr. Med. Nicole Toursarkissian , Berlin , Germany

9. Clinical Pharmacology Department, Hospital Universitario De La Princesa, Instituto de Investigación Sanitaria La Princesa, Universidad Autónoma de Madrid , Madrid , Spain

10. Praxis Dr. Med. Josef Großkopf , Wallerfing , Germany

11. QPS Netherlands B.V. , Groningen , The Netherlands

12. Clinical Research Institute , Minneapolis, Minnesota , USA

13. GSK , Wavre , Belgium

Abstract

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.

Funder

GlaxoSmithKline Biologicals

SA

Publisher

Oxford University Press (OUP)

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