A systems immunology study comparing innate and adaptive immune responses in adults to COVID-19 mRNA (BNT162b2/mRNA-1273) and adenovirus vectored vaccines (ChAdOx1-S) after the first, second and third doses

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 Ghislain Masavuli; Arthur Eng Lip Yeow; Arunasingam Abayasingam; David Agapiou; Hannah Stevens; Jana Zecha; Nicole L. Messina; Nigel C Curtis; Vera Ignjatović; Paul Monagle; Huyen Anh Tran; James D. McFadyen; Rowena Anne Bull; Branka Grubor‐Bauk; Miriam Anne Lynn; Rochelle Botten; Simone E. Barry; David John Lynn

doi:10.1101/2022.09.22.22280180

Genetic & Genomic MedicinemedRxivSep 22, 2022

Preprint

A systems immunology study comparing innate and adaptive immune responses in adults to COVID-19 mRNA (BNT162b2/mRNA-1273) and adenovirus vectored vaccines (ChAdOx1-S) after the first, second and third doses

Feargal J. Ryan iD, Todd S. Norton iD, Conor McCafferty iD, Stephen J. Blake iD, Natalie E. Stevens iD, Jane James iD, Georgina L. Eden iD, Yee C. Tee iD, Saoirse C. Benson iD, Makutiro Ghislain Masavuli iD, Arthur Eng Lip Yeow iD, Arunasingam Abayasingam iD, David Agapiou iD, Hannah Stevens iD, Jana Zecha iD, Nicole L. Messina iD, Nigel C Curtis iD, Vera Ignjatović iD, Paul Monagle iD, Huyen Anh Tran iD, James D. McFadyen iD, Rowena Anne Bull iD, Branka Grubor‐Bauk iD, Miriam Anne Lynn iD, Rochelle Botten, , David John Lynn iD

Abstract

We longitudinally profiled immune responses in 102 adults who received BNT162b2 (Pfizer-BioNTech) or ChAdOx1-S (Oxford-AstraZeneca) as their primary vaccinations. Bloods were collected pre-vaccination, 1-7 days after the 1st, 2nd and 3rd doses (BNT162b2 or mRNA-1273) to assess innate and early adaptive responses, and [~]28 days after the 2nd and 3rd doses to assess immunogenicity. Using a multi-omics approach including RNAseq, cytokine multiplex assay, proteomics, lipidomics, and flow cytometry we identified key differences in the immune responses induced by the ChAdOx1-S and BNT162b2 vaccines that were correlated with subsequent antigen-specific antibody and T cell responses or vaccine reactogenicity. We observed that vaccination with ChAdOx1-S but not BNT162b2 induced a memory-like response after the first dose, which was correlated with the expression of several proteins involved in complement and coagulation. The COVID-19 Vaccine Immune Responses Study (COVIRS) thus represents a major resource to understand the immunogenicity and reactogenicity of these COVID-19 vaccines.

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