COVID-19 has swept across the globe since 2019 and repeated waves of infection have been caused by different variants of the original SARS-CoV-2 (wild type), with the Omicron and Delta variants having dominated recently. Vaccination is among the most important measures in the absence of widespread use of antivirals for prevention of morbidity and mortality. Inactivated virus vaccine has been abundantly used in many countries as the primary two-dose regimen. We aim to study the safety and immunogenicity of CoronaVac (three-dose inactivated virus vaccine) and the BNT162b2 (two-dose inactivated virus vaccine followed by an mRNA vaccine) booster. Both CoronaVac and BNT162b2 boosters are generally safe and have good immunogenicity against the wild type SARS-CoV-2 and the Delta variant with the majority having neutralizing antibodies (NAb) on day 30 and day 90. However, the BNT162b2 booster is associated with a much higher proportion of positive NAb against the Omicron variant. Only 8% of day 30 and day 90 samples post CoronaVac booster have NAb against the Omicron variant. In addition, more BNT162b2 booster recipients are having positive T-cell responses using interferon gamma release assay. In places using inactivated virus vaccine as the primary two-dose scheme, the heterologous mRNA vaccine booster is safe and more immunogenic against the Omicron variant and should be considered as a preferred option during the current outbreak.