Multi-omics analysis reveals COVID-19 vaccine induced attenuation of inflammatory responses during breakthrough disease.

Autor:	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.
Jazyk:	angličtina
Zdroj:	Nature communications [Nat Commun] 2024 Apr 22; Vol. 15 (1), pp. 3402. Date of Electronic Publication: 2024 Apr 22.
DOI:	10.1038/s41467-024-47463-6
Abstrakt:	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).)
Databáze:	MEDLINE
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