Background: To determine the dynamic SARS-CoV-2 specific antibody levels induced by 3 doses of an inactivated COVID-19 vaccine, CoronaVac. An observational, prospective cohort study was performed with 93 healthy healthcare workers from a tertiary hospital in Nanjing, China. Serum SARS-CoV-2 specific IgM, IgG, and neutralizing antibodies (NAb) were measured at different time points among participants who received 3 doses of inactivated COVID-19 vaccine. Results: 91.3% (85/93) and 100% (72/72) participants showed positive both for SARS-CoV-2 specific IgG and NAb after 2-dose CoronaVac and after 3-dose CoronaVac, respectively. Anti-SARS-CoV-2 IgG responses reached 91.21 (55.66–152.06) AU/mL, and surrogate NAb was 47.60 (25.96–100.81) IU/mL on day 14 after the second dose. Anti- SARS-CoV-2 IgG responses reached 218.29 (167.53–292.16) AU/mL and surrogate NAb was 445.54 (171.54–810.90) IU/ mL on day 14 after the third dose. Additionally, SARS-CoV-2 specific surrogate neutralizing antibody titers were highly correlated with serum neutralization activities against Ancestral, Omicron, and Delta strains. Moreover, significantly higher SARS-CoV-2 IgG responses, but not NAb responses, were found in individuals with breakthrough infection when compared to that of 3-dose CoronaVac recipients. Conclusions: CoronaVac elicited robust SARS-CoV-2 specific humoral responses. Surrogate NAb assay might substitute for pseudovirus neutralization assay. Monitoring SARS-CoV-2 antibody responses induced by vaccination would provide important guidance for the optimization of COVID-19 vaccines.
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