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 2 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-receptor-binding domain antibody at 14 days after the booster dose was significantly higher in the heterologous group (11 780.55 binding antibody unit (BAU)/mL [95% CI, 10 891.52-12 742.14]) than in the ChAdOx1 (1561.51 [95% CI, 1415.03-1723.15]) or BNT162b2 (2895.90 [95% CI, 2664.01-3147.98]) groups (both p < 0.001). The neutralizing antibody titer of the heterologous group (geometric mean ND 50 , 2367.74 [95% CI, 1970.03-2845.74]) was comparable to that of the BNT162b2 group (2118.63 [95% CI, 1755.88-2556.32]; p > 0.05) but higher than that of the ChAdOx1 group (391.77 [95% CI, 326.16-470.59]; p < 0.001). 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 ND 50 , 872.01 [95% CI, 685.33-1109.54]), 4.0-fold in the BNT162b2 group (337.93 [95% CI, 262.78-434.57]), and 3.2-fold in the ChAdOx1 group (206.61 [95% CI, 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.
Discussion: 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.
Keywords: BNT162b2; COVID-19; ChAdOx1; Heterologous vaccination; SARS-CoV-2.
【저자키워드】 COVID-19, heterologous vaccination, SARS-CoV-2., BNT162b2, ChAdOx1, 【초록키워드】 SARS-CoV-2, vaccination, immunogenicity, reactogenicity, antibody, Local, delta variant, healthcare worker, Humoral response, HCWs, RBD, SARS-CoV-2 spike protein, Antibody titer, humoral immune response, group, homologous, booster dose, Heterologous, Neutralizing antibody titer, dose, binding antibody, HCW, systemic reactogenicity, domain, participant, wild-type SARS-CoV-2, anti-receptor-binding domain, geometric mean titer, robust, enrolled, evaluated, reduced, significantly higher, comparable, groups, geometric, reactogenicity profile, tolerable, 【제목키워드】 SARS-CoV-2, vaccination, reactogenicity, variant, Neutralizing antibody response, induce, tolerable,