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

Nat Med. 2021 Sep;27(9):1530-1535. doi: 10.1038/s41591-021-01464-w. Epub 2021 Jul 26.

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.

Publication types

  • Observational Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antibodies, Neutralizing / blood*
  • Antibodies, Viral / blood*
  • BNT162 Vaccine
  • CD4 Lymphocyte Count
  • CD4-Positive T-Lymphocytes / immunology
  • CD8-Positive T-Lymphocytes / immunology
  • COVID-19 / immunology
  • COVID-19 / prevention & control
  • COVID-19 Vaccines / immunology*
  • ChAdOx1 nCoV-19
  • Humans
  • Immunization, Secondary / methods*
  • Immunogenicity, Vaccine / immunology
  • Immunoglobulin G / blood
  • SARS-CoV-2 / immunology*
  • Spike Glycoprotein, Coronavirus / immunology
  • Vaccination

Substances

  • Antibodies, Neutralizing
  • Antibodies, Viral
  • COVID-19 Vaccines
  • Immunoglobulin G
  • Spike Glycoprotein, Coronavirus
  • spike protein, SARS-CoV-2
  • ChAdOx1 nCoV-19
  • BNT162 Vaccine