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Immunogenicity and Reactogenicity of Heterologous ChAdOx1 NCoV-19/mRNA Vaccination

Abstract

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.

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References
1.
Voysey M, Clemens S, Madhi S, Weckx L, Folegatti P, Aley P . Safety and efficacy of the ChAdOx1 nCoV-19 vaccine (AZD1222) against SARS-CoV-2: an interim analysis of four randomised controlled trials in Brazil, South Africa, and the UK. Lancet. 2020; 397(10269):99-111. PMC: 7723445. DOI: 10.1016/S0140-6736(20)32661-1. View

2.
Rydyznski Moderbacher C, Ramirez S, Dan J, Grifoni A, Hastie K, Weiskopf D . Antigen-Specific Adaptive Immunity to SARS-CoV-2 in Acute COVID-19 and Associations with Age and Disease Severity. Cell. 2020; 183(4):996-1012.e19. PMC: 7494270. DOI: 10.1016/j.cell.2020.09.038. View

3.
Schmidt T, Klemis V, Schub D, Schneitler S, Reichert M, Wilkens H . Cellular immunity predominates over humoral immunity after homologous and heterologous mRNA and vector-based COVID-19 vaccine regimens in solid organ transplant recipients. Am J Transplant. 2021; 21(12):3990-4002. PMC: 8652989. DOI: 10.1111/ajt.16818. View

4.
Schub D, Klemis V, Schneitler S, Mihm J, Lepper P, Wilkens H . High levels of SARS-CoV-2-specific T cells with restricted functionality in severe courses of COVID-19. JCI Insight. 2020; 5(20). PMC: 7605520. DOI: 10.1172/jci.insight.142167. View

5.
Borobia A, Carcas A, Perez-Olmeda M, Castano L, Bertran M, Garcia-Perez J . Immunogenicity and reactogenicity of BNT162b2 booster in ChAdOx1-S-primed participants (CombiVacS): a multicentre, open-label, randomised, controlled, phase 2 trial. Lancet. 2021; 398(10295):121-130. PMC: 8233007. DOI: 10.1016/S0140-6736(21)01420-3. View