Safety and immunogenicity of homologous versus heterologous booster dose with AZD1222, mRNA-1273, or MVC-COV1901 SARS-CoV-2 vaccines in adults: An observer-blinded, multi-center, phase 2 randomized trial

OBJECTIVES: To report the safety and immunogenicity profile of a protein subunit vaccine (MVC-COV1901) compared to AZD1222 and mRNA-1273 when given as a third (booster) dose to individuals who have completed different primary vaccine regimens. METHODS: Individuals were classified according to their primary vaccine regimens, including two-dose MVC-COV1901, AZD1222, or mRNA-1273. A third dose of either half-dose MVC-COV1901, full-dose MVC-COV1901, standard-dose AZD1222, half-dose mRNA-1273 was administered in a 1:1:1:1 treatment ratio to individuals with an interval range of 84–365 days after the second dose. Endpoints included safety, humoral immunogenicity, and cell-mediated immune response on trial days 15 and 29. Exploratory endpoint included testing against variants of concern (Omicron). RESULTS: Overall, 803 participants were randomized and boosted − 201 received half-dose MVC-COV1901, 196 received full-dose MVC-COV1901, 203 received AZD1222, and 203 received half-dose mRNA-1273. Reactogenicity was mild to moderate, and less in the MVC-COV1901 booster group. Heterologous boosting provided the best immunogenic response. Boosting with mRNA-1273 in MVC-COV1901 primed individuals induced the highest antibody titers, even against Omicron, and cell-mediated immune response. CONCLUSIONS: Overall, MVC-COV1901 as a booster showed the best safety profiles. MVC-COV1901 as a primary series, with either homologous or heterologous booster, elicited the highest immunogenic response. ClinicalTrials.gov registration NCT05197153