Homologous and heterologous boosting of the ChAdOx1-S1-S COVID-19 vaccine with the SCB-2019 vaccine candidate: a randomized, observer-blinded, controlled, phase 2 study

Abstract

Background: Ongoing outbreaks of COVID-19 have been associated with waning immunity following primary immunizations and emergence of new SARS-CoV-2 variants. Heterologous boosters have been suggested to maintain population immunity. Methods: In this study of heterologous boosters we assessed immunogenicity and reactogenicity of booster doses of different formulations of alum-adjuvanted SCB-2019 vaccine (9 μg SCB-2019 with or without CpG-1018 adjuvant, or 30 μg SCB-2019 with CpG-1018) in Brazilian adults primed with ChAdOx1-S vector vaccine. S-protein and ACE2 binding antibodies were measured by ELISA on Days 1, 15 and 29. Participants self-reported solicited adverse events and reactions. Results: All SCB-2019 formulations increased ELISA antibodies against S-protein and ACE2 to a greater extent than ChAdOx1-S. After 30 μg SCB-2019+CpG+alum titers against wild-type S-protein and ACE2 were significantly higher than after ChAdOx1-S on Days 15 and 29, as were GMTs for neutralizing antibodies against wild-type strain and Beta, Gamma, Delta, and Omicron variants. Boosting with SCB-2019 or ChAdOx1-S was well tolerated with no vaccine-related serious or severe adverse events. Conclusions: Heterologous boosting with SCB-2019 of ChAdOx1-S-primed adults was more efficient in increasing immunity against wild-type strain and SARS-CoV-2 variants than a homologous ChAdOx1-S booster, highest responses being with the 30 μg SCB-2019+CpG+alum formulation.