Head-to-head analysis of immunogenicity and reactogenicity of heterologous ChAdOx1 nCoV-19-priming and BNT162b2 or mRNA-1273-boosting with homologous COVID-19 vaccine regimens

Abstract

Head-to-head analyses of immunogenicity and reactogenicity between the authorized homologous vaccine-regimens and heterologous combinations thereof are currently limited. Using a convenience cohort of 331 healthy individuals, we show that humoral and cellular immunity after vaccination with ChAdOx1-nCoV-19 followed by either BNT162b2 (n=66) or mRNA-1273 (n=101) is equivalent or superior to homologous mRNA-regimens (n=43 BNT162b2, n=59 mRNA-1273), and more pronounced than after homologous ChAdOx1-nCoV-19 vaccination (n=62). Levels of spike-specific CD8 T cells were highest in both heterologous regimens, and significantly higher than all three homologous combinations. Among mRNA-containing combinations, spike-specific CD4 T-cell levels in regimens including mRNA-1273 were higher than respective combinations with BNT162b2. Polyfunctional T-cell levels were highest in regimens based on ChAdOx1-nCoV-19-priming. All five regimens were well tolerated with most pronounced reactogenicity upon ChAdOx1-nCoV-19-priming and mRNA-1273-boosting. In conclusion, immunogenicity after heterologous vector/mRNA-boosting and homologous mRNA-regimens is superior to homologous vector-regimens with notable differences between mRNA vaccines.