@article{73a844c1c09048f18df50a527f6f8af6,
title = "A systems immunology study comparing innate and adaptive immune responses in adults to COVID-19 mRNA and adenovirus vectored vaccines",
abstract = "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 = "COVID-19 vaccine, RNA-seq, SARS-CoV-2, T cell, antibody responses, cytokines, immunophenotyping, lipidomics, proteomics, vaccination",
author = "Ryan, {Feargal J.} and Norton, {Todd S.} and Conor McCafferty and Blake, {Stephen J.} and Stevens, {Natalie E.} and Jane James and Eden, {Georgina L.} and Tee, {Yee C.} and Benson, {Saoirse C.} and Masavuli, {Makutiro G.} and Yeow, {Arthur E.L.} and Arunasingam Abayasingam and David Agapiou and Hannah Stevens and Jana Zecha and Messina, {Nicole L.} and Nigel Curtis and Vera Ignjatovic and Paul Monagle and Huyen Tran and McFadyen, {James D.} and Bull, {Rowena A.} and Branka Grubor-Bauk and Lynn, {Miriam A.} and Rochelle Botten and Barry, {Simone E.} and Lynn, {David J.}",
note = "Funding Information: 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. Funding Information: The authors thank all of the study participants. This work was funded by BioPlatforms Australia , the Flinders Foundation , and EMBL Australia Group Leader funding awarded to D.J.L. The proteomics component of this study was funded by AstraZeneca . This work was also supported in part by the MRFF ( APP2015305 ) and The Hospital Research Foundation Group . We thank SA Pathology for help with sample collection and the South Australian Genomics Center (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. We thank the Garvan Institute for providing the sequin controls for RNA sequencing. The MR1 tetramer technology was produced by the NIH Tetramer Core Facility as permitted to be distributed by the University of Melbourne. Flow cytometry analysis was performed at the ACRF Cellular Imaging and Cytometry Core Facility in SAHMRI. We thank Prof. Peter Meikle and Natalie Mellett for their assistance with generating the lipidomics data. Funding Information: The authors thank all of the study participants. This work was funded by BioPlatforms Australia, the Flinders Foundation, and EMBL Australia Group Leader funding awarded to D.J.L. The proteomics component of this study was funded by AstraZeneca. This work was also supported in part by the MRFF (APP2015305) and The Hospital Research Foundation Group. We thank SA Pathology for help with sample collection and the South Australian Genomics Center (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. We thank the Garvan Institute for providing the sequin controls for RNA sequencing. The MR1 tetramer technology was produced by the NIH Tetramer Core Facility as permitted to be distributed by the University of Melbourne. Flow cytometry analysis was performed at the ACRF Cellular Imaging and Cytometry Core Facility in SAHMRI. We thank Prof. Peter Meikle and Natalie Mellett for their assistance with generating the lipidomics data. The study was conceived and designed by D.J.L. F.J.R. performed the multi-omics analyses under the supervision of D.J.L. with input from S.J.B. T.S.N. C.M. and N.E.S.; S.J.B. and N.E.S. generated the flow cytometry data with help from S.C.B.; N.E.S. generated the cytokine data. T.S.N. conducted the T cell ELISpot and AIM assays. J.J. G.L.E. Y.C.T. and M.A.L managed and processed the clinical samples. C.M. V.I. J.Z. and P.M. generated the proteomics data. H.S. H.T. and J.D.M. performed the lipidomics analysis. M.G.M. A.E.L.Y. and B.G.-B. generated the binding antibody data. A.A. A.D. and R.B. generated the NAb data. Sample collection protocols were adapted from protocols originally developed by N.L.M. and N.C. Participant surveys were developed by N.L.M. and N.C.; R.B. and S.E.B. were responsible for participant coordination. The manuscript was written by F.J.R. T.S.N. N.E.S, S.J.B. and D.J.L. with contributions and approval from all the authors. 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. Publisher Copyright: {\textcopyright} 2023 The Author(s)",
year = "2023",
month = mar,
day = "21",
doi = "10.1016/j.xcrm.2023.100971",
language = "English (US)",
volume = "4",
journal = "Cell Reports Medicine",
issn = "2666-3791",
publisher = "Cell Press",
number = "3",
}