Discussion
infection, hypertension
ADENOVIRUS, INFECTION, VIRUS, HYPERTENSION
Here, we have conducted a comprehensive assessment of the reactogenicity, antibody response, T-cell responses and risk of omicron BA.2 infection in a randomised trial of homologous and heterologous boosting with BNT162b2 and CoronaVac, both of which used ancestral virus as the vaccine strain. Our population had minimal COVID-19 history before all three doses of vaccination,Neutralising antibodies were shown to be correlates of protection when comparing mRNA and adenovirus vectored vaccines, and in comparisons between vaccinated and unvaccinated individuals.Our study has several limitations. First, due to logistical challenges, we were only able to randomise at the time vaccination appointment was made, but not at vaccination, and nearly half of randomly assigned individuals dropped out before vaccination. However, the rates of dropout were similar across study groups, and individuals dropping out were not aware of their allocated vaccine type. Comparisons between study groups did not identify significant differences in most baseline characteristics measured, nor any significant differences in antibody and cell-mediated response measured at baseline. Second, there were baseline age differences between the CC-C and CC-B groups, and differences in the proportion of participants with hypertension between the BB-C and BB-B groups, but the differences in neutralising antibodies after third-dose vaccination of CoronaVac versus BNT162b2 remained statistically significant after adjusting for age and hypertension status. Third, we did not include an unvaccinated control group, nor a two-dose comparison group, to evaluate the additional benefits of third dose over existing two doses. Fourth, we have only studied neutralising antibodies and T-cell response, and other branches of immunity, such as non-neutralising antibodies,Most populations received a primary series with mRNA or inactivated COVID-19 vaccines; thus, our findings have wide relevance to booster vaccination policies around the world. Differences in neutralising antibody response are interpreted as indicative of superior efficacy against infection, and have been used as correlate of protection in immunobridging studies for COVID-19 vaccines. The observed discrepancy between neutralising antibody response and vaccine efficacy against infection in our trial might indicate the challenge of using neutralising antibody as the only correlate or mediator of protection against infection,In conclusion, our results suggest there is immune benefit in both administering a homologous or heterologous third dose 6 months after two doses of inactivated or mRNA vaccination, especially in adults who initially received two doses of an inactivated vaccine, with similar levels of protection against infection provided by all four combinations. Mass vaccination programmes that offer both inactivated and mRNA vaccines will allow flexibility in vaccine deployment and encourage vaccine uptake. Our finding that neutralising antibody might not be the dominant correlate of protection for inactivated vaccines, especially against SARS-CoV-2 variants, such as omicron, that have significant capacity to evade neutralising antibody, needs to be considered in the development of variant-proof COVID-19 vaccines or vaccines broadly protective against sarbecoviruses currently in development.