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 μg] and half [15 μg] 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-γ) responses post-booster. AR patients.

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 μg- and 15 μg- BNT162b2 induced the highest anti-RBD IgG concentration (BAU/mL); Coronavac-prime: 30 μg-BNT162b2, 5152.2 (95%CI 4491.7-5909.8); 15 μg-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 μg-BNT162b2, 2363.8 (2005.6-2786.1; 15 μg-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 μg- and 15 μg- 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.

CONCLUSIONS

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.