Safety, reactogenicity, and immunogenicity of Ad26.COV2.S as homologous or heterologous COVID-19 booster vaccination: Results of a randomized, double-blind, phase 2 trial.

ABSTRACT

COVID-19 vaccine boosters may optimize durability of protection against variants of concern (VOCs). In this randomized, double-blind, phase 2 trial, participants received 3 different dose levels of an Ad26.COV2.S booster (5 × 1010 vp [viral particles], 2.5 × 1010 vp, or 1 × 1010 vp) ≥6 months post-primary vaccination with either single-dose Ad26.COV2.S (homologous boost; n = 774) or 2-dose BNT162b2 (heterologous boost; n = 758). Primary endpoints were noninferiority of neutralizing antibody responses at Day 15 post-boost versus Day 29 post-primary vaccination. Secondary endpoints included reactogenicity/safety and neutralizing antibody responses to VOCs. All primary endpoints passed prespecified hierarchical noninferiority criteria by Day 15 post-boost. Geometric mean increases in neutralizing antibody titers against the D614G reference strain ranged from 5.5 to 6.8 at Day 15 for homologous boosting and 12.6 to 22.0 for heterologous boosting. For VOCs, heterologous boosting elicited higher neutralizing antibody responses than homologous boosting. Neutralizing antibody responses were dose-dependent and durable for ≥6 months post-boost. More solicited systemic adverse events occurred following heterologous versus homologous boosting. Trial RegistrationClinicalTrials.gov Identifier NCT04999111.