Respiratory Syncytial Virus Prefusion F Protein Vaccine Is Efficacious in Older Adults With Underlying Medical Conditions
Authors: Feldman Robert G , Antonelli-Incalzi Raffaele , Steenackers Katie , Lee Dong-Gun , Papi Alberto , Ison Michael G , Fissette Laurence , David Marie-Pierre , Maréchal Céline , Van der Wielen Marie , Kostanyan Lusine , Hulstrøm Veronica ,   for the AReSVi-006 Study Group, Adams Mark , Adams Michael , Akite Elaine Jacqueline , Alt Ingrid , Andrews Charles , Asatryan Asmik , Athan Eugene , 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 , Chinsky Kenneth , Choi Melissa , Choo Eun-Ju , Collete Delphine , Corral Carrillo Maria , Davis Matthew G , de Heusch Magali , de Looze Ferdinandus , De Meulemeester Marc , De Negri Ferdinando , De Schrevel Nathalie , DeAtkine David , Dedkova Viktoriya , Descamps Dominique , Dezutter Nancy , Dzongowski Peter , Eckermann Tamara , Essink Brandon , Faulkner Karen , Ferguson Murdo , Fuller Gregory , Galan Melendez Isabel Maria , Gentile Ivan , Ghesquiere Wayne , Grimard Doria , Gruselle Olivier , 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 , Langley Joanne M , Lee Jin-Soo , Leroux-Roels Isabel , Lins Muriel , Lombaard Johannes , Mahomed Akbar , Malerba Mario , Marechal Celine , Martinon-Torres Federico , Martinot Jean-Benoit , Masuet-Aumatell Cristina , McNally Damien , Medina Pech Carlos Eduardo , Mendez Galvan Jorge , 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 , Olivier Aurelie , Orso Maurizio , Ortiz Molina Jacinto , Pak Tatiana , Park Dae Won , Patel Meenakshi , Patel Minesh , Pedro Pijoan Anna Maria , Perez Vera Merce , Perez Alberto Borobia , Perez-Breva Lina , Pileggi Claudia , Pregliasco Fabrizio , Pretswell Carol , Quinn Dean , Reynolds Michele , Romanenko Viktor , Rosen Jeffrey , Roy Nathalie , Ruiz Antoran Belen , Sakata Hideaki , Sauter Joachim , Schaefer Axel , Schwarz Tino F , Sein Anand Izabela , Serra Rexach Jose Antonio , Shu David , Siig Andres , Simon William , Smakotina Svetlana , Stephan Brigitte , Tafuri Silvio , Takazawa Kenji , Tellier Guy , Terryn Wim , Tharenos Leslie , Thomas Nick , Toursarkissian Nicole , Ukkonen Benita , Vale Noah , Van Landegem Pieter-Jan , van Zyl-Smit Richard N , Vanden Abeele Carline , Verheust Celine , Vermeersch Lode , Vicco Miguel , Vitale Francesco , Voloshyna Olga , White Judith , Wie Seong-Heon , Wilson Jonathan , Ylisastigui Pedro 
Published: September 2023

Abstract

Background
Older adults with chronic cardiorespiratory or endocrine/metabolic conditions are at increased risk of respiratory syncytial virus (RSV)-related acute respiratory illness (RSV-ARI) and severe respiratory disease. In an ongoing, randomized, placebo-controlled, multicountry, phase 3 trial in ≥60-year-old participants, an AS01E-adjuvanted RSV prefusion F protein-based vaccine (RSVPreF3 OA) was efficacious against RSV-related lower respiratory tract disease (RSV-LRTD), severe RSV-LRTD, and RSV-ARI. We evaluated efficacy and immunogenicity among participants with coexisting cardiorespiratory or endocrine/metabolic conditions that increase the risk of severe RSV disease (“conditions of interest”).

Methods
Medically stable ≥60-year-old participants received 1 dose of RSVPreF3 OA or placebo. Efficacy against first RSV-LRTD and RSV-ARI episodes was assessed in subgroups with/without coexisting cardiorespiratory or endocrine/metabolic conditions of interest. Immunogenicity was analyzed post hoc in these subgroups.

Results
In total, 12 467 participants received RSVPreF3 OA and 12 499 received placebo. Of these, 39.6% (RSVPreF3 OA) and 38.9% (placebo) had ≥1 coexisting condition of interest. The median efficacy follow-up was 6.7 months. Efficacy against RSV-LRTD was high in participants with ≥1 condition of interest (94.6%), ≥1 cardiorespiratory (92.1%), ≥1 endocrine/metabolic (100%), and ≥2 conditions of interest (92.0%). Efficacy against RSV-ARI was 81.0% in participants with ≥1 condition of interest (88.1% for cardiorespiratory, 79.4% for endocrine/metabolic conditions) and 88.0% in participants with ≥2 conditions of interest. Postvaccination neutralizing titers were at least as high in participants with ≥1 condition of interest as in those without.

Conclusions
RSVPreF3 OA was efficacious against RSV-LRTD and RSV-ARI in older adults with coexisting medical conditions associated with an increased risk of severe RSV disease.

Clinical Trials Registration
ClinicalTrials.gov: NCT04886596.