Bivalent RSVpreF Vaccine in Adults 18 to <60 Years Old With High-Risk Conditions
Matthew Davis, William Towner, Elliot DeHaan, Qin Jiang, Wen Li, Farah Rahman, Michael Quinn Patton, Hayley Wyper, Maria Maddalena Lino, Uzma Sarwar, Zaynah Majid-Mahomed, Saumil Mehta, William Howitt, Kevin Cannon, Elena Kalinina, David Cooper, Kena A. Swanson, Annaliesa S. Anderson, Alejandra Gurtman, Iona Munjal, MONeT Study Team, Natalia Castillo Almeida, Kevin Cannon, William Towner, Joseph Davis, Elissa Malkin, David Diemert, James Clark, Haresh Boghara, Jonathan Cohen, Mary M. Bailey, Matthew W. Doust, Michael Carter, William B. Smith, Maria Onoya, Saumil Mehta, David DeAtkine, Helen Stacey, William Howland, Felipe Suplicy, Michael Dever, Matthew Davis, David Mishkin, Joel Neutel, Ilja Hulinsky, Abid Chaudhry, Erick Stanley Petersen Juárez, Monica Mauri, Jeffrey B. Rosen, William Howitt, Terry Klein, David G. Taylor, Douglas Denham
Abstract
BACKGROUND: Older individuals and adults with certain chronic or immunocompromising health conditions are at increased risk of severe respiratory syncytial virus (RSV) disease. METHODS: In this phase 3 randomized trial of RSVpreF safety and immunogenicity in 18-59-year-olds at high risk of severe RSV disease, participants were randomized 2:1 to 1 RSVpreF (120 µg) or placebo dose. Primary safety endpoints included reactogenicity events and adverse events (AEs) through 7 days and 1 month after vaccination, respectively, and serious AEs (SAEs) and newly diagnosed chronic medical conditions (NDCMCs) throughout the study. In primary analyses, immunogenicity elicited 1 month after RSVpreF was bridged to a randomly selected subset of ≥60-year-olds receiving RSVpreF from the immunogenicity subset in the pivotal phase 3 RENOIR trial, which demonstrated RSVpreF efficacy. Noninferiority was declared if 95% confidence interval (CI) lower bounds were >.667 (neutralizing titer adjusted geometric mean ratios) and >-10% (seroresponse rate differences) for RSV-A and RSV-B. RESULTS: Overall, 678 participants received RSVpreF (n = 453) or placebo (n = 225). Most reactogenicity events were mild/moderate; severe events occurred in ≤2.0% of participants overall. AE frequencies were similar in RSVpreF (7.1%) and placebo recipients (7.6%). No vaccine-related SAEs or NDCMCs were reported. One month after RSVpreF administration, noninferiority criteria were met in 18-59-year-olds versus ≥60-year-olds for RSV-A and RSV-B neutralizing titers and seroresponse rates. CONCLUSIONS: RSVpreF was well tolerated with no safety concerns and demonstrated immunobridging to efficacy in 18-59-year-olds at high risk of severe RSV disease versus ≥60-year-olds in whom efficacy was previously demonstrated, supporting use of RSVpreF to prevent RSV-associated disease in this population. NCT05842967.