Immunogenicity and safety of monovalent and bivalent SARS-CoV-2 variant adapted RBD-based protein booster vaccines in adults previously immunized with different vaccine platforms: A phase II/III, randomized clinical trial.

A randomized, placebo-controlled, crossover, double-blind, phase II/III study was conducted to evaluate the immunogenicity, safety, and tolerability of a recombinant booster vaccine (ARVAC) containing the SARS-CoV-2 spike protein receptor binding domain in three versions: ARVACGamma, ARVACOmicron, and ARVACBivalent in adults with ≤3 previous SARS-CoV-2 booster doses. Primary endpoint was seroconversion rate of neutralizing antibodies compared to placebo and to a > 75 % seroconversion rate to vaccine antigen homologous variants. All vaccine versions significantly increased seroconversion rates to SARS-CoV-2 variants compared to placebo. In participants aged 18-60 years, all versions met the primary endpoint; in those over 60 years old, ARVACOmicron and ARVACBivalent met this endpoint. No vaccine-related serious adverse events were recorded, and most adverse events were mild. Plasma levels of anti-spike-specific IgG and anti-S1-specific IgA in saliva increased in participants receiving any vaccine. The increase in plasma neutralizing antibodies induced by the vaccine was independent of the number of previous booster doses (0, 1 or 2), the primary vaccine platform (adenovirus, single-dose adenovirus, mRNA, inactivated virus, heterologous vaccination, and virus-like particle [VLP]) and the history of previous COVID-19. The neutralizing Ab response induced by the vaccine in healthy participants was similar to that triggered in participants with underlying medical conditions associated with an increased risk of severe COVID-19. ARVACBivalent induced high seroconversion rates (>90 %) against multiple variants and was superior to other ARVAC-versions. It increased neutralizing antibodies against SARS-CoV-2 variants (Ancestral, Gamma, Omicron, XBB and JN.1) and SARS-CoV-1. (NCT05752201).