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Clinical Trial
. 2024 Jun 14;78(6):1732-1744.
doi: 10.1093/cid/ciae010.

Efficacy and Safety of Respiratory Syncytial Virus (RSV) Prefusion F Protein Vaccine (RSVPreF3 OA) in Older Adults Over 2 RSV Seasons

Michael G Ison  1 , Alberto Papi  2 , Eugene Athan  3   4 , Robert G Feldman  5 , Joanne M Langley  6 , Dong-Gun Lee  7 , Isabel Leroux-Roels  8 , Federico Martinon-Torres  9   10   11 , Tino F Schwarz  12 , Richard N van Zyl-Smit  13 , Céline Verheust  14 , Nancy Dezutter  14 , Olivier Gruselle  14 , Laurence Fissette  14 , Marie-Pierre David  14 , Lusine Kostanyan  14 , Veronica Hulstrøm  14 , Aurélie Olivier  14 , Marie Van der Wielen  14 , Dominique Descamps  14 ; AReSVi-006 Study Group
Collaborators, Affiliations
Clinical Trial

Efficacy and Safety of Respiratory Syncytial Virus (RSV) Prefusion F Protein Vaccine (RSVPreF3 OA) in Older Adults Over 2 RSV Seasons

Michael G Ison et al. Clin Infect Dis. .

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.

Keywords: RSV; older adults; respiratory syncytial virus prefusion F protein vaccine.

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Conflict of interest statement

Potential conflicts of interest . M. G. I. declares that research support from GSK was paid to his previous institution, Northwestern University; he received consulting fees from Adagio Therapeutics, ADMA Biologics, Adamis Pharmaceuticals, AlloVir, Atea, Cidara Therapeutics, Genentech/Roche, Janssen, Shionogi, Takeda, Talaris, and Eurofins Viracor; and payment for participating in data safety monitoring boards or advisory boards from Adamis Pharmaceuticals, AlloVir, National Institutes of Health, CSL Behring, Janssen, Merck, Seqirus, Takeda, and Talaris; all of these ended in December 2022; M. G. I. also receives author royalties from UpToDate, which is ongoing, and serves as Chair of the International Society for Influenza and other Respiratory Virus Diseases Antiviral Group and was Editor-in-Chief of Transplant Infectious Disease. A. P. declares funding from GSK for conducting the trial. A. P. also declares that his institution received grants from Chiesi, AstraZeneca, GSK, Sanofi, and Agenzia Italiana del Farmaco; that he received consulting fees from Chiesi, AstraZeneca, GSK, Novartis, Sanofi, Avillion, and ELPEN Pharmaceuticals; payment for participation in advisory boards from Chiesi, AstraZeneca, GSK, Novartis, Sanofi, IQVIA, Avillion, and ELPEN Pharmaceuticals; and honoraria from Chiesi, AstraZeneca, GSK, Menarini, Novartis, Zambon, Mundipharma, Sanofi, Edmond Pharmaceuticals, IQVIA, Avillion, and ELPEN Pharmaceuticals. R. G. F. declares having received payment from GSK for lectures and support for travel related to these activities. J. M. L. reports grants from GSK paid to her institution for the conduct of the trial and from GSK, Pfizer, Merck, Moderna, Sanofi, Inventprise, and VBI Vaccines for other trials; J. M. L. also reports being a board member of Seqirus and participating on a data safety monitoring board or advisory board for Vaxcyte; she is an expert panelist for Canada's Drug and Health Technology Agency for the review of nirsevimab. I. L.-R. declares that her institution received funding from GSK for conducting this trial; from Icosavax, Virometix, Janssen Vaccines, Curevac, Moderna, Osivax, MSD, ICON Genetics, and OSE Immunotherapeutics for other vaccine trials; from Janssen Vaccines and MSD for consulting services; and from Janssen Vaccines for participation on a data safety monitoring board or advisory board. F. M.-T. declares that his institution received payment from GSK for conducting this trial and from Ablynx, Abbott, Seqirus, Sanofi, MSD, Merck, Pfizer, Roche, Regeneron, Janssen, Medimmune, Novavax, Novartis, and GSK for other vaccine trials; F. M.-T. also reports receiving honoraria for lectures from Sanofi, MSD, Moderna, GSK, Biofabri, AstraZeneca, Novavax, Janssen, and Pfizer; payment of travel expenses and meeting fees from Pfizer, MSD, GSK, and Sanofi; and participation on data safety monitoring boards or advisory boards for Pfizer and Biofabri; F. M.-T. is also a member of the World Health Organization’s (WHO's) European Technical Advisory Group of Experts, coordinator of the Spanish Pediatric Clinical Trials Network, and coordinator of the WHO Collaborating Center for Vaccine Safety of Santiago de Compostela. T. F. S. reports honoraria and/or participation on data safety monitoring boards or advisory boards from Alexion, AstraZeneca, Bavarian Nordic, Biogen, Biontech, GSK, Janssen-Cilag, Merck-Serono, Moderna, MSD, Novavax, Pfizer, Roche, Sanofi-Aventis, Seqirus, Synlab, Takeda, and va-Q-tec. R. N. v. Z.-S. reports that his institution received support from Boehringer Ingelheim for the Interstitial Lung Diseases (ILD) registry and that he received consulting fees from GSK and honoraria for lectures from Glenmark, Boehringer Ingelheim, Cipla, and Novartis; R. N. v. Z.-S. also participated on data safety monitoring boards or advisory boards for OnQ SA; he is president of the South African Thoracic Society and co-chair of the International Health Committee of the American Thoracic Society. C. V., N. D., O. G., L. F., M.-P. D., L. K., V. H., A. O., M. V. d. W., and D. D. are employed by GSK and have stock options or shares from GSK. N. D. is co-applicant on a pending patent for vaccination against RSV and has stock options from Haleon. L. F., M.-P. D., A. O., and M. V. d. W. are co-applicants on a pending patent filed by GSK. The other authors report no potential conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed.

Figures

Figure 1.
Figure 1.
Study design. Participants were randomized before RSV season 1 to receive 1 dose of RSV prefusion F protein–based vaccine (RSVPreF3 OA) or placebo. RSVPreF3 OA recipients were re-randomized before RSV season 2 to receive a second RSVPreF3 OA dose (RSV_revaccination group) or placebo (RSV_1dose group). Participants who received placebo pre–season 1 received a second placebo dose pre–season 2. Abbreviations: NH, Northern Hemisphere; RSV, respiratory syncytial virus; SH, Southern Hemisphere.
Figure 2.
Figure 2.
Flow of participants. Abbreviations: ICF, informed consent form; N, number of participants; n, number of participants eliminated; placebo, group of participants randomized to receive placebo pre-season 1 and 2; R, randominzation (1:1); RSV, respiratory syncytial virus; RSV-ARI, RSV-related acute respiratory illness; RSV_1dose, group of participants who received a dose of RSV prefusion F protein-based vaccine (RSVPreF3 OA) pre–season 1 and were randomized to receive a placebo dose pre–season 2; RSVPreF3 OA, group of participants randomized to receive a dose of RSVPreF3 OA pre–RSV season 1; RSV_revaccination, group of participants who received a first dose of RSVPreF3 OA pre–season 1 and were randomized to receive a second RSVPreF3 OA dose (revaccination) pre–season 2.
Figure 3.
Figure 3.
Cumulative incidence of RSV-LRTD over 2 RSV seasons. Analysis includes cases reported from day 15 post–dose 1 until 31 March 2023 for participants who received dose 2 or until 30 September 2022 for those who did not receive dose 2. A, For the analysis of a single vaccine dose, participants who received 2 vaccine doses (RSV_revaccination group) contributed to RSV season 1 but were censored before dose 2 administration. B, For the analysis of the revaccination regimen, participants who received vaccine as dose 1 and placebo as dose 2 (RSV_1dose group) contributed to season 1 but were censored before dose 2 administration. Abbreviations: RSV, respiratory syncytial virus; RSV-LRTD, RSV-related lower respiratory tract disease confirmed by the adjudication committee; RSVPreF3 OA, RSV prefusion F protein–based vaccine.
Figure 4.
Figure 4.
Solicited AEs after a first or second dose of RSVPreF3 OA or placebo. AE rates after dose 1 (RSV season 1) were analyzed in the solicited safety population; AE rates after dose 2 (RSV season 2) were analyzed in the dose 2–solicited safety population. Fever was defined as a temperature ≥38.0°C by any route. Abbreviations: AE, adverse event; CI, confidence interval (depicted as error bars); N, maximum number of participants with solicited safety data available; placebo group, group of participants who received placebo pre–season 1 and pre–season 2; RSV, respiratory syncytial virus; RSV_1dose group, group of participants who received a single RSV prefusion F protein–based vaccine (RSVPreF3) OA dose pre–season 1 and a placebo dose pre–season 2; RSVPreF3 OA group, group of participants who received a dose of RSVPreF3 OA pre–season 1; RSV_revaccination group, group of participants who received a first RSVPreF3 OA dose pre–season 1 and a second RSVPreF3 OA dose (revaccination) pre–season 2.
Figure 5.
Figure 5.
Plain-language summary.
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