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

Ruth E. Drury, Susana Camara, Irina Chelysheva, Sagida Bibi, Katherine Sanders, Salle Felle, Katherine Emary, Daniel Phillips, Merryn Voysey, Daniela M. Ferreira, Paul Klenerman, Sarah C. Gilbert, Teresa Lambe, Andrew J. Pollard and Daniel O’Connor ()
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Ruth E. Drury: University of Oxford
Susana Camara: University of Oxford
Irina Chelysheva: University of Oxford
Sagida Bibi: University of Oxford
Katherine Sanders: University of Oxford
Salle Felle: University of Oxford
Katherine Emary: University of Oxford
Daniel Phillips: University of Oxford
Merryn Voysey: University of Oxford
Daniela M. Ferreira: University of Oxford
Paul Klenerman: NIHR Oxford Biomedical Research Centre
Sarah C. Gilbert: NIHR Oxford Biomedical Research Centre
Teresa Lambe: University of Oxford
Andrew J. Pollard: University of Oxford
Daniel O’Connor: University of Oxford

Nature Communications, 2024, vol. 15, issue 1, 1-18

Abstract: 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.

Date: 2024
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DOI: 10.1038/s41467-024-47463-6

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