Immunogenicity and safety in healthy adults of full dose versus half doses of COVID-19 vaccine (ChAdOx1-S or BNT162b2) or full-dose CoronaVac administered as a booster dose after priming with CoronaVac: a randomised, observer-masked, controlled trial in Indonesia

Inactivated COVID-19 vaccines effectively prevent death, but their effectiveness for preventing infection or severe illness is known to decrease within 3–6 months following the second priming dose. Here we aimed to evaluate the immunogenicity and safety of three potential booster vaccines administered as a full-dose homologous booster or full-dose or half-dose heterologous boosters among individuals primed with CoronaVac. We did an observer and participant masked, randomised controlled trial study of healthy Indonesian adults from five recruitment sites in Bandung and Jakarta, Indonesia, aged 18 years and older who had previously received two doses of CoronaVac within 3 to less than 6 months or 6 to 9 months before the booster dose. Participants were randomly assigned (1:1:1:1:1) by means of stratified randomisation with random block size to a homologous booster with full-dose CoronaVac or heterologous boosters with ChAdOx1-S or BNT162b2 in full dose or half dose. The primary outcome was to evaluate the seropositive, seroconversion rate, and the geometric mean titres of IgG anti-spike-receptor binding domain and neutralising antibodies, 28 days after booster dose vaccination in the per-protocol population. Safety was assessed as a secondary outcome in all vaccinated booster participants by the incidence rate and intensity of adverse events within 24 h, 7 days, and 28 days after the booster dose. This study is registered with ina-registry.org, INA-GO0HLGB, and is complete. Between Nov 26 and Dec 16, 2021, 1015 people were screened, and 960 healthy adults were enrolled; 190–193 were included in each group. 28 days after receiving the booster, combining the 3 to less than 6 months and 6 to 9 months groups, the proportions of seroconversion rates in each vaccine group were ChAdOx1-S 75 (82%) of 92 to 87 (88%) of 99 for full dose and half dose, BNT162b2 92 (92%) of 100 to 90 (98%) of 92 for full dose and half dose, and CoronaVac in 38 (41%) of 92 to 65 (66%) of 98. All booster groups achieved 100% seropositivity 28 days after the booster dose. Participants in the 6 to 9 months priming group achieved higher titres compared with participants in the 3 to less than 6 months priming group. The geometric mean titres in participants in the 6 to 9 months priming group in each vaccine group were ChAdOx1-S 11258·69 (9562·43–13 255·85) and 7853·04 (6698·92–9206·00) for full dose and half dose, BNT162b2 19999·84 (17 720·58–22 572·25) and 17 017·62 (14 694·40–19 708·16) for