Efficacy and Safety of Respiratory Syncytial Virus (RSV) Prefusion F Protein Vaccine (RSVPreF3 OA) in Older Adults Over 2 RSV Seasons
Michael G. Ison, Alberto Papi, Eugene Athan, Robert G. Feldman, Joanne M. Langley, Dong‐Gun Lee, Isabel Leroux‐Roels, Federico Martinón‐Torres, Tino F. Schwarz, Richard N. van Zyl-Smit, Céline Verheust, Nancy Dezutter, Olivier Gruselle, Laurence Fissette, Marie‐Pierre David, Lusiné Kostanyan, Veronica Hulstrøm, Aurélie Olivier, Marie Van der Wielen, Dominique Descamps, for the AReSVi-006 Study Group, Mark N. Adams, Michael L. Adams, Clara Agutu, Elaine Jacqueline Akité, Ingrid Alt, Charles P. Andrews, Rafaelle Antonelli-Incalzi, Asmik Asatryan, Ghazaleh Bahrami, Elena Bargagli, Qasim Bhorat, Paul Bird, Przemysław Borowy, Céline Boutry, Carles Brotons Cuixart, David Browder, Judith C. Brown, Erik Buntinx, Donald P. Cameron, Laura Cámpora, Cyrille Cartier, Kenneth Chinsky, Melissa Choi, Eun Ju Choo, Delphine Collete, Maria Corral Carrillo, Susanna Cuadripani, Matthew Davis, Magali de Heusch, Ferdinandus de Looze, Marc De Meulemeester, Ferdinando De Negri, Nathalie De Schrevel, David DeAtkine, Viktoriya Dedkova, Peter Dzongowski, Tamara Eckermann, Brandon Essink, Karen Faulkner, Murdo Ferguson, Gregory N. Fuller, Isabel Maria Galan Melendez, Ivan Gentile, Wayne Ghesquière, Doria Grimard, Scott A. Halperin, Amardeep Heer, Laura Helman, Andre Hotermans, Tomáš Jelı́nek, Jackie Kamerbeek, Hyo Youl Kim, Murray Kimmel, Mark Koch, Satu Kokko, Susanna Koski, Shady Kotb, Antonio Lalueza, Jin Soo Lee, Muriel Lins, Johannes Lombaard, Akbar Mahomed, Mario Malerba, Céline Maréchal, Sandie Marion, Jean‐Benoît Martinot, Cristina Masuet‐Aumatell, Damien McNally, Carlos Eduardo Medina Pech, J M Gonzalez Galvan, Lise Mercati, Narcisa Mesaros, Dieter Mesotten, Essack Mitha, Kathryn Mngadi, Beate Moeckesch, Barnaby Montgomery, Linda Murray, Rhiannon Nally
Abstract
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.