Immunogenicity and reactogenicity of heterologous ChAdOx1 nCoV-19/mRNA vaccination

In healthy adults, booster vaccination with an mRNA vaccine, irrespective of the vaccine used for the first dose, was well tolerated and elicited higher levels of spike-specific antibodies and spike-specific T cells than booster vaccination with ChAdOx1 nCov-19. Heterologous priming with the ChAdOx1 nCoV-19 vector vaccine followed by boosting with a messenger RNA vaccine (BNT162b2 or mRNA-1273) is currently recommended in Germany, although data on immunogenicity and reactogenicity are not available. In this observational study we show that, in healthy adult individuals (n = 96), the heterologous vaccine regimen induced spike-specific IgG, neutralizing antibodies and spike-specific CD4 T cells, the levels of which which were significantly higher than after homologous vector vaccine boost (n = 55) and higher or comparable in magnitude to homologous mRNA vaccine regimens (n = 62). Moreover, spike-specific CD8 T cell levels after heterologous vaccination were significantly higher than after both homologous regimens. Spike-specific T cells were predominantly polyfunctional with largely overlapping cytokine-producing phenotypes in all three regimens. Recipients of both the homologous vector regimen and the heterologous vector/mRNA combination reported greater reactogenicity following the priming vector vaccination, whereas heterologous boosting was well tolerated and comparable to homologous mRNA boosting. Taken together, heterologous vector/mRNA boosting induces strong humoral and cellular immune responses with acceptable reactogenicity profiles.

Automated summary

In healthy adults, vaccination with an mRNA vaccine as a booster, regardless of the initial vaccine, resulted in higher levels of spike-specific antibodies and T cells compared to booster vaccination with ChAdOx1 nCov-19. Heterologous vaccination with ChAdOx1 nCoV-19 followed by an mRNA vaccine induced strong immune responses with acceptable reactogenicity, showing similar or better effects than homologous mRNA vaccine regimens.