A systems immunology study comparing innate and adaptive immune responses in adults to COVID-19 mRNA and adenovirus vectored vaccines

Feargal J. Ryan, Todd S. Norton, Conor McCafferty, Stephen J. Blake, Natalie E. Stevens, Jane James, Georgina L. Eden, Yee C. Tee, Saoirse C. Benson, Makutiro G. Masavuli, Arthur E.L. Yeow, Arunasingam Abayasingam, David Agapiou, Hannah Stevens, Jana Zecha, Nicole L. Messina, Nigel Curtis, Vera Ignjatovic, Paul Monagle, Huyen TranJames D. McFadyen, Rowena A. Bull, Branka Grubor-Bauk, Miriam A. Lynn, Rochelle Botten, Simone E. Barry, David J. Lynn

Research output: Contribution to journalArticlepeer-review

11 Citations (Scopus)


Identifying the molecular mechanisms that promote optimal immune responses to coronavirus disease 2019 (COVID-19) vaccination is critical for future rational vaccine design. Here, we longitudinally profile innate and adaptive immune responses in 102 adults after the first, second, and third doses of mRNA or adenovirus-vectored COVID-19 vaccines. Using a multi-omics approach, we identify key differences in the immune responses induced by ChAdOx1-S and BNT162b2 that correlate with antigen-specific antibody and T cell responses or vaccine reactogenicity. Unexpectedly, we observe that vaccination with ChAdOx1-S, but not BNT162b2, induces an adenoviral vector-specific memory response after the first dose, which correlates with the expression of proteins with roles in thrombosis with potential implications for thrombosis with thrombocytopenia syndrome (TTS), a rare but serious adverse event linked to adenovirus-vectored vaccines. The COVID-19 Vaccine Immune Responses Study thus represents a major resource that can be used to understand the immunogenicity and reactogenicity of these COVID-19 vaccines.

Original languageEnglish
Article number100971
JournalCell Reports Medicine
Issue number3
Publication statusPublished or Issued - 21 Mar 2023


  • COVID-19 vaccine
  • RNA-seq
  • SARS-CoV-2
  • T cell
  • antibody responses
  • cytokines
  • immunophenotyping
  • lipidomics
  • proteomics
  • vaccination

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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