Immunogenicity and safety of SARS-CoV-2 recombinant protein vaccine (CHO cell) LYB001 as a heterologous booster following two- or three-dose inactivated COVID-19 vaccine in adults aged ≥18 years: interim results of a randomized, active-controlled, double-blinded, phase 3 trial.

Background: LYB001 is a recombinant protein COVID-19 vaccine displaying a receptor-binding domain (RBD) in a highly immunogenic array on virus-like particles (VLPs). This study assessed the immunogenicity and safety of LYB001 as a booster.

Research design and methods: In this randomized, active-controlled, double-blinded, phase 3 trial, participants aged ≥ 18 years received a booster with LYB001 or ZF2001 (Recombinant COVID-19 Vaccine). The primary endpoint was to compare the geometric mean titer (GMT) of neutralizing antibodies against Omicron BA.4/5 at 14 days after the booster.

Results: Overall, 1,200 participants aged ≥ 18 years were enrolled, 599 received LYB001, and 601 received ZF2001. Based on similar baseline level, the 14-day GMT ratio (LYB001/ZF2001) against Omicron BA.4/5 was 1.39 (95% CI: 1.25, 1.56), demonstrating superiority (95% CI lower limit > 1) of LYB001. The spike protein-binding IgG concentrations induced by LYB001 were significantly higher than those induced by ZF2001 on day 14 and day 28 after the booster (p-value <0.0001). LYB001 recipients reported more adverse reactions than ZF2001 recipients (21.4% vs. 15.0%); however, all adverse reactions in the LYB001 group were mild-to-moderate.

Conclusions: LYB001 is highly immunogenic and retains a well-characterized safety profile in adults aged ≥ 18 years.

Clinical trial registration: www.clinicaltrials.gov, identifier is NCT05664932.