The immunogenicity and reactogenicity of four COVID-19 booster vaccinations against SARS-CoV-2 variants following CoronaVac or ChAdOx1 nCoV-19 primary series

Background: The appropriate COVID-19 booster vaccine following inactivated or adenoviral vector COVID-19 vaccination is unclear. Objective: To investigate the immunogenicity of four COVID-19 booster vaccines. Methods: We prospectively enrolled healthy adults who received a two-dose CoronaVac or ChAdOx1 8-12 weeks earlier and allocated them to receive one of the following booster vaccine: inactivated (BBIBP-CorV), ChAdOx1 or mRNA (BNT162b2 at full [30 mu g] and half [15 mu g] dose) vaccines. We determined the reactogenicity and the humoral (anti-receptor binding domain IgG (anti-RBD-IgG), neutralizing antibodies (nAb) against Delta, Beta and Omicron variants) and cellular immunity measuring by interferon gamma (IFN-gamma) responses post-booster. Results: Among the 352 participants (179 CoronaVac and 173 ChAdOx1 participants), 285 (81%) were female, and median age was 39 (IQR: 31-47) years. Two weeks post-booster, both 30 mu g- and 15 mu g- BNT162b2 induced the highest anti-RBD IgG concentration (BAU/mL); Coronavac-prime: 30 mu g-BNT162b2, 5152.2 (95%CI 4491.7-5909.8); 15 mu g-BNT162b2, 3981.1 (3397.2-4665.4); ChAdOx1, 1358.0 (1141.8-1615.1); BBIBP-CorV, 154.6 (92.11-259.47); ChAdOx1-prime: 30 mu g-BNT162b2, 2363.8 (2005.6-2786.1; 15 mu g-BNT162b2, 1961.9 (1624.6-2369.1); ChAdOx1, 246.4 (199.6-304.2); BBIBP-CorV, 128.1 (93.5-175.4). Similarly, both 30 mu g- and 15 mu g- BNT162b2 boosting induced the highest nAb titers against Beta, Delta and Omicron BA.1 variants and highest T-cell response at 2 weeks after boosting. While all BNT162b2 or heterologous ChAdOx1-boosted participants had nAb against Omicron, these were < 50% for BBIBP-CorV and 75% for homologous ChAdOx1-boosted participants. There was significant decrease in nAb (> 4-fold) at 16-20 weeks post booster for all groups. Conclusion: Heterologous boosting with BNT162b2 following CoronaVac or ChAdOx1 primary series is most immunogenic. Additional studies are needed to verify the clinical efficacy and persistence of immunity following half-dose BNT162b2.