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Multi-omics analysis reveals COVID-19 vaccine induced attenuation of inflammatory responses during breakthrough disease.
Drury, Ruth E; Camara, Susana; Chelysheva, Irina; Bibi, Sagida; Sanders, Katherine; Felle, Salle; Emary, Katherine; Phillips, Daniel; Voysey, Merryn; Ferreira, Daniela M; Klenerman, Paul; Gilbert, Sarah C; Lambe, Teresa; Pollard, Andrew J; O'Connor, Daniel.
Affiliation
  • Drury RE; Oxford Vaccine Group, Department of Paediatrics, University of Oxford, Oxford, UK.
  • Camara S; NIHR Oxford Biomedical Research Centre, Oxford, UK.
  • Chelysheva I; Oxford Vaccine Group, Department of Paediatrics, University of Oxford, Oxford, UK.
  • Bibi S; NIHR Oxford Biomedical Research Centre, Oxford, UK.
  • Sanders K; Oxford Vaccine Group, Department of Paediatrics, University of Oxford, Oxford, UK.
  • Felle S; NIHR Oxford Biomedical Research Centre, Oxford, UK.
  • Emary K; Oxford Vaccine Group, Department of Paediatrics, University of Oxford, Oxford, UK.
  • Phillips D; NIHR Oxford Biomedical Research Centre, Oxford, UK.
  • Voysey M; Oxford Vaccine Group, Department of Paediatrics, University of Oxford, Oxford, UK.
  • Ferreira DM; NIHR Oxford Biomedical Research Centre, Oxford, UK.
  • Klenerman P; Oxford Vaccine Group, Department of Paediatrics, University of Oxford, Oxford, UK.
  • Gilbert SC; NIHR Oxford Biomedical Research Centre, Oxford, UK.
  • Lambe T; Oxford Vaccine Group, Department of Paediatrics, University of Oxford, Oxford, UK.
  • Pollard AJ; NIHR Oxford Biomedical Research Centre, Oxford, UK.
  • O'Connor D; Oxford Vaccine Group, Department of Paediatrics, University of Oxford, Oxford, UK.
Nat Commun ; 15(1): 3402, 2024 Apr 22.
Article de En | MEDLINE | ID: mdl-38649734
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.
Sujet(s)

Texte intégral: 1 Collection: 01-internacional Base de données: MEDLINE Sujet principal: Vaccins contre la COVID-19 / COVID-19 / Vaccin ChAdOx1 nCoV-19 / Réinfections Limites: Adult / Female / Humans / Male / Middle aged Langue: En Journal: Nat Commun Sujet du journal: BIOLOGIA / CIENCIA Année: 2024 Type de document: Article Pays de publication: Royaume-Uni

Texte intégral: 1 Collection: 01-internacional Base de données: MEDLINE Sujet principal: Vaccins contre la COVID-19 / COVID-19 / Vaccin ChAdOx1 nCoV-19 / Réinfections Limites: Adult / Female / Humans / Male / Middle aged Langue: En Journal: Nat Commun Sujet du journal: BIOLOGIA / CIENCIA Année: 2024 Type de document: Article Pays de publication: Royaume-Uni