Heterologous vaccination for COVID19. Heterologous immunization with inactivated vaccine followed by mRNA booster elicits strong humoral and cellular immune responses against the SARS-CoV-2 Omicron variant

The recent emergence of the Omicron variant has strengthened concerns on vaccine efficacy and the urgent need to study more efficient vaccination strategies. Here we evaluated the effect of mRNA vaccine booster on immunogenicity in individuals who had been vaccinated with two doses of inactivated vaccines. We observed that an mRNA vaccine booster significantly increased the level of plasma-specific antibodies that bind to the RBD domain of the G614 (6.3-fold) and the Omicron variant 9.9-fold) compared to two doses of homologous inactivated vaccine. The RBD-specific IgG antibody and neutralization titers in the heterologous vaccination group were similar to that in individuals receiving three doses of homologous mRNA vaccines or mRNA vaccine after infection. Moreover, this heterologous vaccination regime significantly enhanced the number of RBD-specific memory B cells and S1-specific T cells compared to two doses of homologous inactivated vaccine. Our study demonstrates that an mRNA vaccine booster in individuals vaccinated with inactivated vaccines can be highly beneficial, as it markedly increases the humoral and cellular immune response against the Omicron variant.