Efficacy and Safety of Respiratory Syncytial Virus (RSV) Prefusion F Protein Vaccine (RSVPreF3 OA) in Older Adults Over 2 RSV Seasons
Authors: Ison Michael G , Papi Alberto , Athan Eugene , Feldman Robert G , Langley Joanne M , Lee Dong-Gun , Leroux-Roels Isabel , Martinon-Torres Federico , Schwarz Tino F , van Zyl-Smit Richard N , Verheust Céline , Dezutter Nancy , Gruselle Olivier , Fissette Laurence , David Marie-Pierre , Kostanyan Lusine , Hulstrøm Veronica , Olivier Aurélie , Van der Wielen Marie , Descamps Dominique ,   for the AReSVi-006 Study Group, Adams Mark , Adams Michael , Agutu Clara , Akite Elaine Jacqueline , Alt Ingrid , Andrews Charles , Antonelli-Incalzi Rafaelle , Asatryan Asmik , Bahrami Ghazaleh , Bargagli Elena , Bhorat Qasim , Bird Paul , Borowy Przemyslaw , Boutry Celine , Brotons Cuixart Carles , Browder David , Brown Judith , Buntinx Erik , Cameron Donald , Campora Laura , Cartier Cyrille , Chinsky Kenneth , Choi Melissa , Choo Eun-Ju , Collete Delphine , Corral Carrillo Maria , Cuadripani Susanna , Davis Matthew G , de Heusch Magali , de Looze Ferdinandus , De Meulemeester Marc , De Negri Ferdinando , de Schrevel Nathalie , DeAtkine David , Dedkova Viktoriya , Dzongowski Peter , Eckermann Tamara , Essink Brandon , Faulkner Karen , Ferguson Murdo , Fuller Gregory , Galan Melendez Isabel Maria , Gentile Ivan , Ghesquiere Wayne , Grimard Doria , Halperin Scott , Heer Amardeep , Helman Laura , Hotermans Andre , Jelinek Tomas , Kamerbeek Jackie , Kim Hyo Youl , Kimmel Murray , Koch Mark , Kokko Satu , Koski Susanna , Kotb Shady , Lalueza Antonio , Lee Jin-Soo , Lins Muriel , Lombaard Johannes , Mahomed Akbar , Malerba Mario , Marechal Celine , Marion Sandie , Martinot Jean-Benoit , Masuet-Aumatell Cristina , McNally Damien , Medina Pech Carlos Eduardo , Mendez Galvan Jorge , Mercati Lise , Mesaros Narcisa Elena , Mesotten Dieter , Mitha Essack , Mngadi Kathryn , Moeckesch Beate , Montgomery Barnaby , Murray Linda , Nally Rhiannon , Narejos Perez Silvia , Newberg Joseph , Nugent Paul , Ochoa Mazarro Dolores , Oda Harunori , Orso Maurizio , Ortiz Molina Jacinto , Pak Tatiana , Park Dae Won , Patel Meenakshi , Patel Minesh , Pedro Pijoan Anna Maria , Perez Alberto Borobia , Perez-Breva Lina , Perez Vera Merce , Pileggi Claudia , Pregliasco Fabrizio , Pretswell Carol , Quinn Dean , Reynolds Michele , Romanenko Viktor , Rosen Jeffrey , Roy Nathalie , Ruiz Antoran Belen , Sahakyan Vardine , Sakata Hideaki , Sauter Joachim , Schaefer Axel , Sein Anand Izabela , Serra Rexach Jose Antonio , Shu David , Siig Andres , Simon William , Smakotina Svetlana , Steenackers Katie , Stephan Brigitte , Tafuri Silvio , Takazawa Kenji , Tellier Guy , Terryn Wim , Tharenos Leslie , Thomas Nick , Toursarkissian Nicole , Ukkonen Benita , Vale Noah , Van Landegem Pieter-Jan , Vanden Abeele Carline , Vermeersch Lode , Vitale Francesco , Voloshyna Olga , White Judith , Wie Seong-Heon , Wilson Jonathan , Ylisastigui Pedro , Zocco Manuel 
Published: January 2024

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 &gt;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.