Heterologous ChAdOx1 nCoV-19 and BNT162b2 prime-boost vaccination elicits potent neutralizing antibody responses and T cell reactivity

Heterologous COVID-19 vaccination regimens combining vector- and mRNA-based vaccines are already administered, but data on solicited adverse reactions, immunological responses and elicited protection are limited. We aimed to evaluate the reactogenicity, humoral and cellular immune responses towards different SARS-CoV-2 variants after a heterologous ChAdOx1 nCoV-19 BNT162b2 prime-boost vaccination and analyzed a cohort of 26 individuals aged 25-46 (median 30.5) years that received a ChAdOx1 nCoV-19 prime followed by a BNT162b2 boost after an 8- week interval. Self-reported solicited symptoms after ChAdOx1 nCoV-19 prime were in line with previous reports and less severe after the BNT162b2 boost. Antibody titers increased significantly over time resulting in strong neutralization titers two weeks after the BNT162b2 boost. Neutralizing activity against the prevalent strain B.1.1.7 (Alpha) and immune-evading VOC B.1.351 (Beta) was ∼4-fold higher than in individuals receiving homologous BNT162b2 vaccination. No difference was seen in neutralization of VOI B.1.617 (Kappa). In addition, the heterologous vaccination induced CD4+ and CD8+ T cells reactive to SARS-CoV-2 spike peptides of all analyzed variants; Wuhan-Hu-1, B.1.1.7, B.1.351, and P.1 (Gamma). In conclusion, heterologous ChAdOx1 nCoV-19 / BNT162b2 prime-boost vaccination regimen is not associated with serious adverse events and results in a potent humoral immune response and elicits T cell reactivity. Variants B.1.1.7, B.1.351 and B.1.617.1 are potently neutralized by sera of all participants and reactive T cells recognize spike peptides of all tested variants. These results suggest that this heterologous vaccination regimen is at least as immunogenic and protective as homologous vaccinations.