Heterologous ChAdOx1 and BNT162b2 vaccination induces strong neutralizing antibody responses against SARS-CoV-2 including delta variant with tolerable reactogenicity

Abstract

Objectives: We assessed humoral responses and reactogenicity following the heterologous vaccination compared to the homologous vaccination groups.

Methods: 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). Immunogenicity was assessed by measuring antibody titers against receptor-binding domain (RBD) of SARS-CoV-2 spike protein in all participants and neutralizing antibody titer in 100 participants per group. Reactogenicity was evaluated by a questionnaire-based survey.

Results: We enrolled 499 HCWs (ChAdOx1, n=199; BNT162b2, n=200; heterologous ChAdOx1/BNT162b2, n=100). The geometric mean titer of anti-RBD antibody at 14 days after the booster dose was significantly higher in the heterologous group (11780.55 BAU/mL [95% CI, 10891.52-12742.14]) than in the ChAdOx1 (1561.51 [1415.03-1723.15]) or BNT162b2 (2895.90 [2664.01-3147.98]) groups (both P value<.001). The neutralizing antibody titer of the heterologous group (geometric mean ND50, 2367.74 [1970.03-2845.74]) was comparable to that of the BNT162b2 group (2118.63 [1755.88-2556.32], P >.05) but higher than that of the ChAdOx1 group (391.77 [326.16-470.59], P value<.001). Compared with those against wild-type SARS-CoV-2, the geometric mean neutralizing antibody titers against the delta variant at 14 days after the boosting were reduced by 3.0-fold in the heterologous group (geometric mean ND50. 872.01 [95% CI, 685.33-1109.54]), 4.0-fold in the BNT162b2 group (337.93 [262.78-434.57]), and 3.2-fold in the ChAdOx1 group (206.61 [144.05-296.34]). 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: 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.