Superior Boosting of Neutralizing Titers Against Omicron SARS-CoV-2 Variants by Heterologous SCB-2019 Vaccine vs a Homologous Booster in CoronaVac-Primed Adults

Abstract Background We compared homologous and heterologous boosting in adults in the Philippines primed with 2 or 3 doses of CoronaVac, with recombinant protein vaccine, SCB-2019. Methods CoronaVac-immunized adults (18–72 years) received a homologous or heterologous full or half dose SCB-2019 booster. We assessed all neutralizing antibody (NAb) responses against prototype SARS-CoV-2 after 15 days and NAb against SARS-CoV-2 Delta and Omicron variants in subsets (30‒50 per arm). Participants recorded adverse events. Results In 2-dose CoronaVac-primed adults prototype NAb geometric mean titers (GMT) were 203 IU/mL (95% confidence interval [CI], 182–227) and 939 IU/mL (95% CI, 841–1049) after CoronaVac and SCB-2019 boosters; the GMT ratio (4.63; 95% CI, 3.95–5.41) met predefined noninferiority and post-hoc superiority criteria. After 3-dose CoronaVac-priming prototype NAb GMTs were 279 IU/mL (95% CI, 240–325), 1044 IU/mL (95% CI, 898–1213), and 668 IU/mL (95% CI, 520–829) following CoronaVac, full and half-dose SCB-2019 boosters, respectively. NAb GMT ratios against Delta and Omicron comparing SCB-2019 with CoronaVac were all greater than 2. Mild to moderate reactogenicity was evenly balanced between groups. No vaccine-related serious adverse events were reported. Conclusions Full or half dose SCB-2019 boosters were well tolerated with superior immunogenicity than homologous CoronaVac, particularly against newly emerged variants. Clinical Trials Registration. NCT05188677. We compared heterologous boosting with SCB-2019 recombinant protein vaccine with homologous boosting in adults primed with 2–3 doses of CoronaVac vaccine. Heterologous boosting elicited superior neutralizing antibody responses against prototype SARS-CoV-2 and Delta and Omicron variants than homologous boosting.