The emergence of variants of concerns of SARS-CoV-2 highlights the need for comprehensively elucidating the correlates of protection for different COVID-19 vaccine types. Inactivated COVID-19 vaccines are currently amongst the most widely administered vaccines globally. However, investigations into the correlates of protection for inactivated COVID-19 vaccines are relatively rare.

Data from a phase III double-blind, randomized, placebo-controlled clinical trial (NCT0445659) that evaluated the efficacy and safety of the CoronaVac vaccine in healthcare professionals were utilized in this secondary analysis. Additionally, the correlation between neutralizing antibody levels measured by micro-cytopathic effect (CPE) neutralization assay and the occurrence of laboratory-confirmed infections was assessed using neutralizing antibodies measured in blood samples collected on day 28 after receiving two doses of the vaccine. Finally, the protective threshold required to provide 50% protection against symptomatic illness and virus infections was estimated.

The risk of infection was negatively correlated with the levels of post-vaccination neutralizing antibodies measured on day 28 after the second dose. A neutralization titer of 30 (95% CI: 2–56) was predicted to provide 50% efficacy against symptomatic infection, whilst a titer of 42 (95% CI: 24–62) was predicted to provide 50% efficacy against total infection. Lastly, a neutralization titer of 247 (95% CI: 139–506) or higher was required to achieve 80% or higher protection against symptomatic infections.

The results highlight the value of neutralizing antibody response as a correlate of protection, which can be used to inform future vaccine development and implementation. Further studies of immune correlates of protection for other vaccines are warranted.