Efficacy, safety, and immunogenicity of the AS01E-adjuvanted respiratory syncytial virus prefusion F protein vaccine (RSVPreF3 OA) in older adults over three respiratory syncytial virus seasons (AReSVi-006): a multicentre, randomised, observer-blinded, placebo-controlled, phase 3 trial
- PMID: 40245915
- DOI: 10.1016/S2213-2600(25)00048-7
Efficacy, safety, and immunogenicity of the AS01E-adjuvanted respiratory syncytial virus prefusion F protein vaccine (RSVPreF3 OA) in older adults over three respiratory syncytial virus seasons (AReSVi-006): a multicentre, randomised, observer-blinded, placebo-controlled, phase 3 trial
Abstract
Background: Duration of protection after respiratory syncytial virus (RSV) vaccination is unknown. This study aimed to evaluate efficacy and safety over three RSV seasons of the AS01E-adjuvanted RSV prefusion F protein-based vaccine (RSVPreF3 OA) against RSV-related lower respiratory tract disease (RSV-LRTD) in older adults.
Methods: In this randomised, observer-blind, placebo-controlled, phase 3 trial (AReSVi-006), participants aged 60 years or older in 275 centres (ie, GP practices and clinical research sites) across 17 countries in Africa, Asia, Oceania, Europe, and North America were randomly assigned (1:1) to receive RSVPreF3 OA or placebo before RSV season one. RSVPreF3 OA recipients were re-randomly assigned (1:1) before RSV season two to receive a second RSVPreF3 OA dose (RSV revaccination group) or placebo (RSV single-dose group). Recipients of placebo before RSV season one also received placebo before season two (placebo group). The primary objective (efficacy against first occurrence of RSV-LRTD over one RSV season) was reported previously. Confirmatory secondary objectives were to demonstrate efficacy over three RSV seasons of a single RSVPreF3 OA dose and of a first dose followed by revaccination 1 year later, against RSV-LRTD, overall and by RSV subtype (success criteria: lower limits of two-sided CIs around efficacy estimates >20% [RSV-LRTD] and >0% [RSV-LRTD by RSV subtype]). This study is registered with ClinicalTrials.gov, NCT04886596, and is complete.
Findings: Participants were enrolled between May 25, 2021, and Jan 31, 2022. Efficacy analyses included 12 468 RSVPreF3 OA recipients and 12 498 placebo recipients. Cumulative efficacy over three seasons of one RSVPreF3 OA dose was 62·9% (97·5% CI 46·7-74·8) against RSV-LRTD, 69·8% (42·2-85·7) against RSV A-related LRTD, and 58·6% (35·9-74·1) against RSV B-related LRTD (median follow-up from day 15 post-dose one 30·6 months [IQR 26·2-32·0]). Efficacy was observed over three seasons among participants aged 60-69 years, participants aged 70-79 years, pre-frail participants (ie, those with a walking speed of 0·4-0·99 m/s in a gait speed test), and participants with pre-existing conditions that increase the RSV-LRTD risk. Efficacy against RSV-LRTD decreased over time. A first RSVPreF3 OA dose followed by revaccination 1 year later had an efficacy that was within the same range as that of one dose. RSVPreF3 OA showed a clinically acceptable safety profile. Between dose one and trial end, eight (<1%) participants in the RSV single-dose group, 12 (<1%) in the RSV revaccination group, and 12 (<1%) in the placebo group had a serious adverse event considered to be related to the trial intervention by the investigator. Five deaths were assessed as related to the trial intervention by the investigator: three in the vaccine groups (cardiopulmonary failure, cardiac arrest, and left ventricular failure) and two in the placebo group (death of unknown cause and pulmonary embolism).
Interpretation: A single RSVPreF3 OA dose was efficacious against RSV-LRTD over three RSV seasons in people aged 60 years or older, despite a decrease in efficacy over time. Further research is needed to establish the optimal revaccination strategy. These results support the favourable benefit-risk profile of RSVPreF3 OA to help protect against RSV-LRTD for at least three RSV seasons.
Funding: GSK.
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Conflict of interest statement
Declaration of interests MGI declares that research support from GSK was paid to his previous institution, Northwestern University; he received consulting fees paid by Adagio Therapeutics, ADMA Biologics, Adamis Pharmaceuticals, AlloVir, Atea, Cidara Therapeutics, Genentech/Roche, Janssen, Shionogi, Takeda, Talaris, and Eurofins Viracor; and payment for participation 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. MGI 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. MGI's involvement was separate from his government service, and the comments are his own. MGI was a consultant for Romark but received no consulting fees. AP declares funding from GSK for conducting the trial; grants paid to his institution from GSK, Chiesi, AstraZeneca, Sanofi, and Agenzia Italiana del Farmaco; consulting fees from GSK, Chiesi, AstraZeneca, Sanofi, Novartis, Avillion, ELPEN Pharmaceuticals, Zambon, and Edmond Pharma; payment for participation in advisory boards from GSK, Chiesi, AstraZeneca, Sanofi, Novartis, Avillion, ELPEN Pharmaceuticals, Zambon, Edmond Pharma, and IQVIA; and honoraria from GSK, Chiesi, AstraZeneca, Sanofi, Novartis, Avillion, ELPEN Pharmaceuticals, Menarini, Zambon, Mundipharma, Edmond Pharma, and IQVIA. RGF declares having received payment from GSK for congress and speaking events lectures and support for travel related to these activities. JML reports grants paid to her institution from GSK, Pfizer, Merck, Moderna, Sanofi, Inventprise, and VBI Vaccines for conducting trials; and participation on a data safety monitoring board or advisory board for Vaxcyte, Sanofi, GSK, Merck, and Seqirus. IL-R declares grants or research support paid to her institution from GSK, Icosavax, Janssen Vaccines, Curevac, Moderna, Osivax, MSD, and OSE Immunotherapeutics for conducting trials; and payment for participation on a data safety monitoring board or advisory board from Janssen Vaccines and MSD. FM-T declares grants or research support payments to his institution from GSK, Sanofi, Moderna, MSD, Novavax, and Pfizer for conducting vaccine trials; and consulting fees or participation on advisory boards for GSK, Sanofi, MSD, Moderna, AstraZeneca, Biofabri, CSL-Seqirus, Novavax, and Janssen. TFS reports participation on data safety monitoring boards or advisory boards from AstraZeneca, Bavarian Nordic, Biogen, BioNTech, CSL-Seqirus, CSL-Vifor, Diasorin, GSK, Janssen-Cilag, Merck-Serono, Moderna, MSD, Novavax, Pfizer, Roche, Sanofi-Aventis, Synlab, and Takeda. RNvZ-S reports that his institution received support from Boehringer Ingelheim for the Interstitial Lung Disease registry and consulting fees from GSK and honoraria for lectures from Glenmark, Boehringer Ingelheim, Cipla, and Novartis; and payment for participation on data safety monitoring boards or advisory boards for OnQ SA. SC, QD, ND, CG, LF, SX, M-PD, AO, MVdW, and DD are employed by GSK; SC, QD, ND, CG, LF, M-PD, AO, MVdW, and DD hold financial equities in GSK. ND is co-applicant on a pending patent for vaccination against RSV and a patent regarding methods for eliciting an immune response to RSV and Streptococcus pneumoniae infections. MVdW has stock options from Haleon. LF, M-PD, AO, and MVdW are part of vaccine patents filed by GSK. The authors declare no other financial or non-financial relationships. EA and D-GL declare no competing interests.
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