Heterologous Prime-boost of SARS-CoV-2 inactivated vaccine and mRNA BNT162b2 among Healthy Thai Adolescents

Background: Heterologous prime-boost SARS-CoV-2 vaccination is a widely accepted strategy during the COVID-19 pandemic, which generated a superior immune response than homologous vaccination strategy. Objective: To describe immunogenicity of heterologous prime-boost vaccination with inactivated vaccine, CoronaVac, followed by BNT162b2 and 5-month booster dose with BNT162b2 in healthy Thai adolescents. Methods: Adolescents aged 12-18 years were randomized 1:1:1:1 to receive CoronaVac (SV) followed by BNT162b2 (PZ) 30 or 20 lg at either 3- or 6-week interval (SV3w/PZ30lg, SV3w/PZ20lg, SV6w/PZ30lg or SV6w/PZ20lg). During the Omicron-predominant period, participants were offered a BNT162b2 booster dose 30, 15, or 10 lg. Immunogenicity was determined using IgG antibody against spike-receptorbinding domain of wild type(anti-S-RBD IgG) and surrogate virus neutralization test(sVNT) against Delta variant at 14 days and 5 months after the 2nd dose. Neutralization tests(sVNT and pseudovirus neutralization test; pVNT) against Omicron strain were tested pre- and 14 days post-booster dose. Results: In October 2021, 76 adolescents with a median age of 14.3 years (IQR 12.7-16.0) were enrolled: 20 in SV3w/PZ30lg; 17 in SV3w/PZ20lg; 20 in SV6w/PZ30lg; 19 in SV6w/PZ20lg. At day 14, the geometric mean(GM) of anti-S-RBD IgG in SV3w/PZ30lg was 4713 (95 %CI 4127-5382) binding-antibody unit (BAU)/ml, while geometric mean ratio(GMR) was 1.28 (1.09-1.51) in SV6w/PZ30lg. The GMs of sVNT against Delta variants at day 14 among participants in SV3w/PZ30lg and SV6wk/PZ30lg arm were 95.3 % and 99.7 %inhibition, respectively. At 5 months, GMs of sVNT against Delta variants in SV3w/ PZ30lg were significantly declined to 47.8 % but remained at 89.0 % inhibition among SV6w/PZ30lg arm. In April 2022, 52 adolescents received a BNT162b2 booster dose. Proportion of participants with sVNT against Omicron strain > 80 %inhibition was significantly increased from 3.8 % pre-booster to 67 % post-booster. Proportion of participants with pVNT ID50 > 185 was 42 % at 14 days post 2nd dose and 88 % post booster, respectively.