AbstractTo compare the reactogenicity and immunogenicity between the two‐dose mRNA COVID‐19 vaccine regimen and one or two doses of inactivated vaccine followed by an mRNA vaccine regimen in healthy children between 5 and 11 years of age, a prospective cohort study was performed at King Chulalongkorn Memorial Hospital in Thailand between March to June 2022. Healthy children between 5 and 11 years of age were enrolled and received the two‐dose mRNA COVID‐19 vaccine (BNT162b2) regimen or the inactivated (CoronaVac) vaccine followed by the BNT162b2 vaccine regimen. In addition, healthy children who received two doses of BBIBP‐CorV between 1 and 3 months prior were enrolled to receive a heterologous BNT162b2 as a third dose (booster). Reactogenicity was assessed by a self‐reported online questionnaire. Immunogenicity analysis was performed to determine binding antibodies to wild‐type SARS‐CoV‐2. Neutralizing antibodies to Omicron variants (BA.2 and BA.5) were tested using the focus reduction neutralization test. Overall, 166 eligible children were enrolled. Local and systemic adverse events which occurred within 7 days after vaccination were mild to moderate and well‐tolerated. The two‐dose BNT162b2, CoronaVac followed by BNT162b2, and two‐dose BBIBP‐CorV followed by BNT162b2 groups elicited similar levels of anti‐receptor‐binding domain (RBD) IgG. However, the two‐dose BNT162b2 and two‐dose BBIBP‐CorV followed by BNT162b2 groups elicited higher neutralizing activities against the Omicron BA.2 and BA.5 variant than the CoronaVac followed by BNT162b2 group. The CoronaVac followed by BNT162b2 group elicited low neutralizing activities against the Omicron BA.2 and BA.5 variant. A third dose (booster) mRNA vaccine should be prioritized for this group.