It remains unknown whether the Indonesian healthcare workers (HCWs) who had received two doses of CoronaVac vaccine and one dose of mRNA-1273 booster could be protected during the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron wave. In total, 125 infection-naïve and 10 previously infected HCWs were recruited. The mRNA-1273 booster substantially increased titer of anti-SARS-CoV-2 spike protein receptor-binding domain antibodies. However, the monitoring revealed that 34 out of 125 infection-naïve (27.2%) and 3 out of 10 previously infected HCWs (30.0%) were infected during the Omicron wave. All infected HCWs were either asymptomatic or having mild coronavirus disease 2019 (COVID-19) and subsequently fully recovered, supporting the heterologous prime-boost strategy against COVID-19.

Purpose: This study was performed to investigate humoral immune response and adverse events upon the heterologous prime-boost with a single dose of the mRNA-1273 vaccine among fully CoronaVac-vaccinated, infection-naïve healthcare workers in Indonesia. Materials and Methods: One hundred twenty-five eligible healthcare workers were recruited from one hospital for this prospective cohort study. Blood collection was conducted twice, i.e., on 7 days before and 28 days after the booster vaccination. The titer of anti-SARS-CoV-2 receptor-binding domain (RBD) antibodies was quantified accordingly. The post-vaccination adverse event was recorded for both CoronaVac and mRNA-1273 vaccinations. Any breakthrough infection was monitored during the follow-up period. Wilcoxon matched-pairs signed rank test was used to test differences between groups. Results: A significant increase was observed in the titer of anti-SARS-CoV-2 RBD antibodies upon receiving the mRNA-1273 booster (geometric mean titers of 65.57 and 47,445 U/mL in pre- and post-booster, respectively), supporting the argument to use heterologous prime-boost vaccination to improve the protection against COVID-19 in a high-risk population. The mRNA-1273 vaccine, however, caused a higher frequency of adverse events than the CoronaVac vaccine. Nonetheless, the adverse events were considered minor medical events and temporary as all subjects were not hospitalized and fully recovered. Of note, no breakthrough infection was observed during the follow-up to 12 weeks post-booster. Conclusion The heterologous prime-boost vaccination of healthcare workers with a single dose of the mRNA-1273 vaccine generated a significant elevation in humoral immune response towards RBD of SARS-CoV-2 and was associated with a higher frequency, but minor and transient, adverse events.