Immunogenicity of fractional and standard dose COVID-19 vaccine boosters among healthy adults in Indonesia: twenty four month follow-up from a randomised controlled trial.

Although many high-income countries have regular COVID-19 vaccine booster schedules, there are limited data on the protective effects of some heterologous booster combinations. This observational follow-up study of a double blind randomised controlled parallel group trial evaluates long-term immunogenicity, safety and breakthrough infections to 24 months after booster doses (fractional or standard Pfizer BNT162b2, fractional or standard AstraZeneca ChAdOx1, and standard dose CoronaVac) following CoronaVac and AstraZeneca primary series in healthy adults in Indonesia. Of 1,289 trial participants, 962 (75%) complete follow-up to 24 months. Among CoronaVac-primed participants, responses are lower for fractional than standard dose Pfizer at 28 days (binding IgG geometric mean ratio: 0.75, 95% CI: 0.63-0.90), but differences diminish by 12 and 24 months. AstraZeneca-primed participants have lower initial responses than CoronaVac-primed participants following Pfizer and AstraZeneca boosters. Breakthrough infections occurred in >40% of participants between six and 12 months, and in >35% between 12 and 24 months. Fractional and standard doses of AstraZeneca and Pfizer among CoronaVac-primed or AstraZeneca-primed participants, boost immune responses to 24 months. However, fractional doses elicit lower initial responses than standard doses. These findings provide important information for booster strategies, especially in populations primed with inactivated vaccines. Funding: Coalition for Epidemic Preparedness Innovations (CEPI). Trial registration: ina-registry.org , INA-GO0HLGB.