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

https://doi.org/10.1016/j.xcrm.2023.100971Get rights and content
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Highlights

  • Multi-omics profiling of responses in 102 adults after COVID-19 vaccination

  • Baseline and innate responses correlate with vaccine immunogenicity/reactogenicity

  • ChAdOx1-S, but not BNT162b2, induces an adenoviral memory response after the first dose

  • ChAdOx1-S memory response correlates with expression of pro-thrombotic proteins

Summary

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.

Keywords

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

Data and code availability

  • RNASeq data have been deposited at GEO and are publicly available as of the date of publication. Proteomics data have been deposited to the ProteomeXchange Consortium via the PRIDE partner repository are publicly available as of the date of publication. Accession numbers are listed in the key resources table. Supplementary data have been deposited at Mendeley. The DOI is listed in the key resources table. All the multi-omics datasets (Proteomic, lipidomic, serology, flow cytometry, multiplex immunoassay) are available via the Lynn Laboratory BitBucket (https://bitbucket.org/lynnlab/covirs).

  • This paper does not report original code.

  • Any additional information required to reanalyze the data reported in this paper is available from the lead contact upon request.

Cited by (0)

15

These authors contributed equally

16

Lead contact