ABSTRACT
The advent of Omicron variant globally hastened the requirement of a booster vaccination dose to confer continuous protection against symptomatic SARS-CoV2 infection. However, different vaccines are available in different countries and individuals who had adverse reactions to certain vaccine types require heterologous vaccine boosters. To understand the efficacy of different vaccination regimens in inducing humoral responses to SARS-CoV2, we examined plasma antibodies and frequencies of Omicron RBD-specific B cells in individuals who had different priming-booster vaccination regimens. We found that individuals with three homologous doses of mRNA vaccines had higher levels of IgG of all subclasses against RBD of Omicron than individuals with three homologous doses of inactivated virus vaccine. More importantly, individuals who received a booster dose of mRNA vaccine, regardless of the types of priming vaccine, had antibodies with higher neutralizing capability against the Omicron variant. Corroborating the antibody results, boosting with the mRNA vaccine increased the frequencies of Omicron RBD-binding B cells. Together, our data demonstrate that an mRNA vaccine (BNT162b2 or mRNA-1273) booster enhances humoral responses against Omicron variant in individuals vaccinated with either two prior doses of mRNA or inactivated virus vaccine (CoronaVac or BBIBP-CorV), potentially providing more effective protection against SARS-CoV-2 infection, particularly by the Omicron variant.