Immunogenicity and safety of boosting with a recombinant two-component SARS-CoV-2 vaccine: two randomized, parallel-controlled, phase 2 studies

Abstract

ABSTRACT Background Recombinant protein vaccines play a crucial role in providing broad immuno-protection against SARS-CoV-2 variants. This study evaluates the safety and immunogenicity of ReCOV as a booster dose in two randomized, observer-blinded, active-controlled Phase 2 clinical trials. Research design and methods In Study-1, adults who had received two or three doses of inactivated COVID-19 vaccine were randomized (1:1:1) to receive 20 μg ReCOV, 40 μg ReCOV, or an inactivated vaccine (COVILO®) in the United Arab Emirates. Study-2 involved subjects who received two doses of inactivated COVID-19 vaccine and were randomized (1:1:1) to receive 20 μg ReCOV (pilot batch, ReCOV HA), 20 μg ReCOV (commercial batch, ReCOV TC), or 30 μg BNT162b2 (COMIRNATY®) in the Philippines. The primary immunogenicity objectives were to compare geometric mean titer (GMT) and seroconversion rate (SCR) of live-virus neutralizing antibodies against SARS-CoV-2 prototype induced by one booster dose of ReCOV with that of inactivated vaccine and BNT162b2, respectively, at 14 days post-booster. Results Heterologous booster doses of ReCOV were safe, well-tolerated, and elicited noninferior immunogenic responses to inactivated vaccines and BNT162b2 against both Omicron variants and prototype in previously vaccinated adults. The results demonstrated significant advantages in cross-neutralization activities against multiple SARS-CoV-2 variants, surpassing those observed with inactivated vaccines and BNT162b2. Additionally, good immune persistence was noted. Conclusions Heterologous boosting with ReCOV proved safe and effective, with promising results in managing the COVID-19 epidemic. The study sheds light on the high potential of ReCOV in providing enhanced protection, supported by strong cross-neutralization activities and immune persistence. Clinical Trial Registration Study-1, www.clinicaltrials.gov, identifier is NCT05323435; Study-2, www.clinicaltrials.gov, identifier is NCT05084989.