학술논문
Multi-omics analysis reveals COVID-19 vaccine induced attenuation of inflammatory responses during breakthrough disease.
Document Type
Academic Journal
Author
Drury RE; Oxford Vaccine Group, Department of Paediatrics, University of Oxford, Oxford, UK.; NIHR Oxford Biomedical Research Centre, Oxford, UK.; Camara S; Oxford Vaccine Group, Department of Paediatrics, University of Oxford, Oxford, UK.; NIHR Oxford Biomedical Research Centre, Oxford, UK.; Chelysheva I; Oxford Vaccine Group, Department of Paediatrics, University of Oxford, Oxford, UK.; NIHR Oxford Biomedical Research Centre, Oxford, UK.; Bibi S; Oxford Vaccine Group, Department of Paediatrics, University of Oxford, Oxford, UK.; NIHR Oxford Biomedical Research Centre, Oxford, UK.; Sanders K; Oxford Vaccine Group, Department of Paediatrics, University of Oxford, Oxford, UK.; NIHR Oxford Biomedical Research Centre, Oxford, UK.; Felle S; Oxford Vaccine Group, Department of Paediatrics, University of Oxford, Oxford, UK.; NIHR Oxford Biomedical Research Centre, Oxford, UK.; Emary K; Oxford Vaccine Group, Department of Paediatrics, University of Oxford, Oxford, UK.; NIHR Oxford Biomedical Research Centre, Oxford, UK.; Phillips D; Oxford Vaccine Group, Department of Paediatrics, University of Oxford, Oxford, UK.; NIHR Oxford Biomedical Research Centre, Oxford, UK.; Voysey M; Oxford Vaccine Group, Department of Paediatrics, University of Oxford, Oxford, UK.; NIHR Oxford Biomedical Research Centre, Oxford, UK.; Ferreira DM; Oxford Vaccine Group, Department of Paediatrics, University of Oxford, Oxford, UK.; NIHR Oxford Biomedical Research Centre, Oxford, UK.; Department of Clinical Sciences, Liverpool School of Tropical Medicine, Liverpool, UK.; Klenerman P; NIHR Oxford Biomedical Research Centre, Oxford, UK.; Peter Medawar Building for Pathogen Research, Nuffield Dept. of Clinical Medicine, University of Oxford, Oxford, UK.; Translational Gastroenterology Unit, Nuffield Department of Medicine, University of Oxford, Oxford, UK.; Gilbert SC; NIHR Oxford Biomedical Research Centre, Oxford, UK.; Pandemic Sciences Institute, Nuffield Department of Medicine, University of Oxford, Oxford, UK.; Chinese Academy of Medical Science (CAMS) Oxford Institute, University of Oxford, Oxford, UK.; Lambe T; Oxford Vaccine Group, Department of Paediatrics, University of Oxford, Oxford, UK.; NIHR Oxford Biomedical Research Centre, Oxford, UK.; Chinese Academy of Medical Science (CAMS) Oxford Institute, University of Oxford, Oxford, UK.; Pollard AJ; Oxford Vaccine Group, Department of Paediatrics, University of Oxford, Oxford, UK.; NIHR Oxford Biomedical Research Centre, Oxford, UK.; O'Connor D; Oxford Vaccine Group, Department of Paediatrics, University of Oxford, Oxford, UK. daniel.oconnor@paediatrics.ox.ac.uk.; NIHR Oxford Biomedical Research Centre, Oxford, UK. daniel.oconnor@paediatrics.ox.ac.uk.
Source
Publisher: Nature Pub. Group Country of Publication: England NLM ID: 101528555 Publication Model: Electronic Cited Medium: Internet ISSN: 2041-1723 (Electronic) Linking ISSN: 20411723 NLM ISO Abbreviation: Nat Commun Subsets: MEDLINE
Subject
Language
English
Abstract
The immune mechanisms mediating COVID-19 vaccine attenuation of COVID-19 remain undescribed. We conducted comprehensive analyses detailing immune responses to SARS-CoV-2 virus in blood post-vaccination with ChAdOx1 nCoV-19 or a placebo. Samples from randomised placebo-controlled trials (NCT04324606 and NCT04400838) were taken at baseline, onset of COVID-19-like symptoms, and 7 days later, confirming COVID-19 using nucleic amplification test (NAAT test) via real-time PCR (RT-PCR). Serum cytokines were measured with multiplexed immunoassays. The transcriptome was analysed with long, short and small RNA sequencing. We found attenuation of RNA inflammatory signatures in ChAdOx1 nCoV-19 compared with placebo vaccinees and reduced levels of serum proteins associated with COVID-19 severity. KREMEN1, a putative alternative SARS-CoV-2 receptor, was downregulated in placebo compared with ChAdOx1 nCoV-19 vaccinees. Vaccination ameliorates reductions in cell counts across leukocyte populations and platelets noted at COVID-19 onset, without inducing potentially deleterious Th2-skewed immune responses. Multi-omics integration links a global reduction in miRNA expression at COVID-19 onset to increased pro-inflammatory responses at the mRNA level. This study reveals insights into the role of COVID-19 vaccines in mitigating disease severity by abrogating pro-inflammatory responses associated with severe COVID-19, affirming vaccine-mediated benefit in breakthrough infection, and highlighting the importance of clinically relevant endpoints in vaccine evaluation.
(© 2024. The Author(s).)
(© 2024. The Author(s).)