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.

V.I., P.M. and C.M. received funding from AstraZeneca to undertake the proteomics component of this study. J.Z. is an employee of, and holds or may hold stock, in AstraZeneca. All other authors declare no competing interests

This work was funded by BioPlatforms Australia, Flinders Foundation and EMBL Australia Group Leader funding awarded to DJL. The proteomics component of this study was funded by AstraZeneca. This work was also supported in part by a MRFF Coronavirus research response grant (APP2015305) and The Hospital Research Foundation Group COVID-19-SA grant. We thank SA Pathology for help with sample collection and the South Australian Genomics Centre (SAGC) for help with RNA sequencing. The SAGC is supported by the National Collaborative Research Infrastructure Strategy (NCRIS) via BioPlatforms Australia and by the SAGC partner institutes.

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The details of the IRB/oversight body that provided approval or exemption for the research described are given below:

Ethics committee of CALHN Human Research Ethics Committee, Adelaide, Australia gave ethical approval for this work (Approval No. 14778).

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I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance).

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Multi-omics datasets and R code are available via the Lynn Laboratory BitBucket (https://bitbucket.org/lynnlab/covirs). RNASeq data have been deposited in the Gene Expression Omnibus (GEO) under accession GSE199750. The mass spectrometry proteomics data have been deposited to the ProteomeXchange Consortium via the PRIDE partner repository with the dataset identifier PXD036608

https://bitbucket.org/lynnlab/covirs