Safety, Immunogenicity, and Regimen Selection of Ad26.RSV.preF-based Vaccine Combinations: A Randomized, Double-blind, Placebo-Controlled, Phase 1/2a Study.

BACKGROUND

Ad26.RSV.preF is an adenovirus serotype 26 vector-based RSV vaccine encoding a pre-fusion conformation-stabilized RSV fusion protein (preF) that demonstrated robust humoral and cellular immunogenicity and showed promising efficacy in a human challenge study in younger adults. Addition of recombinant RSV preF protein might further enhance RSV-specific humoral immune responses, especially in older populations.

METHODS

This randomized, double-blind, placebo-controlled phase 1/2a study (NCT03502707; https://www.clinicaltrials.gov/ct2/show/NCT03502707) compared the safety and immunogenicity of Ad26.RSV.preF alone and varying doses of Ad26.RSV.preF/RSV preF protein combinations in adults aged ≥60 years. This report includes data from Cohort 1 (initial safety; n=64) and Cohort 2 (regimen selection; n=288). Primary immunogenicity and safety analyses were performed 28 days post-vaccination (Cohort 2) for regimen selection.

RESULTS

All vaccine regimens were well tolerated, with similar reactogenicity profiles between regimens. Combination regimens induced greater humoral (virus-neutralizing and preF-specific binding antibodies) and similar cellular (RSV-F-specific T cells) immune responses compared with Ad26.RSV.preF alone. Vaccine-induced immune responses remained above baseline up to 1.5 years post-vaccination.

CONCLUSIONS

All Ad26.RSV.preF-based regimens were well tolerated. A combination regimen comprising both Ad26.RSV.preF, which elicits strong humoral and cellular responses, and RSV preF protein, which increases humoral responses, was selected for further development.

Informations de copyright

© The Author(s) 2023. Published by Oxford University Press on behalf of Infectious Diseases Society of America.