Objectives: There are limited data on the immunogenicity and reactogenicity of the heterologous vaccination regimen of ChAdOx1 followed by BNT162b2 against SARS-CoV-2, especially the delta variant (B.1.617.2).
Methods: In this prospective cohort study, we enrolled healthcare workers (HCWs) who were either vaccinated with ChAdOx1 followed by BNT162b2 (heterologous group) or two doses of ChAdOx1 (ChAdOx1 group) or BNT162b2 (BNT162b2 group). We evaluated the immunogenicity by measuring the quantitative antibodies against receptor-binding domain (RBD) of SARS-CoV-2 spike protein and plaque reduction neutralizing antibody test (PRNT) against SARS-CoV-2 including the delta variant, and the reactogenicity by a questionnaire-based survey.
Results: We enrolled 499 HCWs (ChAdOx1, n=199; BNT162b2, n=200; heterologous ChAdOx1/BNT162b2, n=100). The mean titer of anti-RBD antibody at 14 days after the booster dose was significantly higher in the heterologous group (12546 BAU/mL) than in the ChAdOx1 (1981 BAU/mL, P<.001) or BNT162b2 (3418 BAU/mL, P<.001) groups. The mean neutralizing antibody titer of the heterologous group (mean ND50 2368) was comparable to that of the BNT162b2 group (mean ND50 2135, P=.37) but higher than that of the ChAdOx1 group (mean ND50 393, P<.001). Compared with those against wild-type SARS-CoV-2, the mean neutralizing antibody titers against the delta variant were reduced by 3.0-fold in the heterologous group (mean ND50 872), 4.0-fold in the BNT162b2 group (mean ND50 338), and 3.2-fold in the ChAdOx1 group (mean ND50 207). The local or systemic reactogenicity after the booster dose in the heterologous group was higher than that of the ChAdOx1 group but comparable to that of the BNT162b2 group.
Conclusions and Relevance:: Heterologous ChAdOx1 followed by BNT162b2 vaccination with a 12-week interval induced a robust humoral immune response against SARS-CoV-2 including the delta variant that was comparable to the homologous BNT162b2 vaccination and stronger than the homologous ChAdOx1 vaccination, with a tolerable reactogenicity profile.