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

We compared homologous and heterologous boosting in adults primed with whole-virus inactivated COVID-19 vaccine, CoronaVac, with recombinant protein vaccine, SCB-2019, to overcome waning vaccine-derived immunogenicity and "vaccine evasion" by SARS-CoV-2 variants. We randomized adults (18-72 years) in the Philippines previously immunized with two or three CoronaVac doses to receive homologous or heterologous full or half doses of SCB-2019 boosters. We assessed non-inferiority/superiority of neutralizing antibody (NAb) responses against prototype SARS-CoV-2 after 15 days and NAb against a panel of SARS-CoV-2 Delta and Omicron variants in subsets (30‒50 per arm). Participants recorded solicited, unsolicited and serious adverse events. In 2-dose CoronaVac-primed adults prototype NAb geometric mean titers (GMT) were 203 IU/mL (95% CI: 182-227) and 939 IU/mL (841-1049) after CoronaVac and SCB-2019 boosters; the GMT ratio (4.63 [3.95-5.41]) met pre-defined non-inferiority and post hoc superiority criteria. In 3-dose CoronaVac-immunized adults NAb GMTs against prototype were 279 IU/mL (240-325), 1044 IU/mL (898-1213), and 668 IU/mL (520-829) after CoronaVac, full and half dose SCB-2019 boosters, respectively. NAb GMT ratios against Delta and Omicron variants comparing full or half SCB-2019 doses with CoronaVac were all greater than 2. Reactogenicity consisted mainly of mild-moderate injection site pain, and mild-moderate headache and fatigue, evenly balanced between groups. No vaccine-related serious adverse events were reported. Boosting CoronaVac-immunized adults with full or half doses of SCB-2019 was well tolerated with superior immunogenicity than homologous boosting, particularly against newly emerged variants, supporting use of SCB-2019 for booster vaccination.