COVID-19 vaccination is associated with attenuation of inflammatory responses during breakthrough disease [small RNA-Seq]
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ABSTRACT: A subset of individualsenrolledina randomised controlled trial ofChAdOx1 nCoV-19 and received either ChAdOx1 COVID-19 or control MenACWY vaccine whoexperienced COVID-19-associated symptoms were evaluated using multi-omictechnologies. Participants were selected to represent symptomatic individuals with and without COVID-19 as determined by a nucleic acid amplification test (NAAT) for stage 1 and only NAAT+ve for stage 2 of the study.
Project description:A subset of individualsenrolledina randomised controlled trial ofChAdOx1 nCoV-19 and received either ChAdOx1 COVID-19 or control MenACWY vaccine whoexperienced COVID-19-associated symptoms were evaluated using multi-omictechnologies. Participants were selected to represent symptomatic individuals with and without COVID-19 as determined by a nucleic acid amplification test (NAAT) for stage 1 and only NAAT+ve for stage 2 of the study.
Project description:A subset of individualsenrolledina randomised controlled trial ofChAdOx1 nCoV-19 and received either ChAdOx1 COVID-19 or control MenACWY vaccine whoexperienced COVID-19-associated symptoms were evaluated using multi-omictechnologies. Participants were selected to represent symptomatic individuals with and without COVID-19 as determined by a nucleic acid amplification test (NAAT).
Project description:Fifty healthcare workers (HCW) who had received Mycobacterium-w (Mw) and at least one dose of ChAdOx1 nCoV-19 vaccine subsequently (Mw+ChAdOx1 group) were monitored for symptomatic COVID-19, during a major outbreak with the delta variant of SARS-CoV-2 (April-June, 2021) in India, along with 201 HCW receiving both doses of the vaccine without Mw (ChAdOx1 group). Bulk RNA-Seq analysis was carried out on 4 subjects enrolled from each group.
Project description:ChAdOx1 nCoV-19, a chimpanzee adenovirus (ChAd)-vector vaccine expressing the SARS-CoV-2 spike protein, has elicited robust immunological responses in large populations. Despite its proven efficacy and safety, some recipients have reported immediate inflammatory reactions post-vaccination. We comprehensively examined the immune landscape following ChAdOx1 nCoV-19 vaccination based on the epigenomic profiles of monocytes. Glucocorticoids are wildly used as steroid anti-inflammatory drugs to modify acute and chronic inflammation. Recently, dexamethasone is used to modify inflammation in COVID19 and side-effects after COVID19 vaccination. ChAdox1 nCoV-19 induces interferon responses and inflammation in human. In addition to IFNa, TNF and IL1b treatment to mimic inflammatory environment gives general effects of glucocorticoids in complex inflammatory context.
Project description:Among new vaccine technologies contributed to the control of the COVID-19 pandemic, ChAdOx1 nCoV-19, a chimpanzee adenovirus (ChAd)-vector vaccine expressing the SARS-CoV-2 spike protein, could be administered globally owing to its low production cost and lack of a requirement for frozen storage. Despite its benefits, most recipients have reported immediate inflammatory reactions after the initial dose vaccination. We comprehensively examined the immune landscape following ChAdOx1 nCoV-19 vaccination based on the single-cell transcriptomes of immune cells and epigenomic profiles of monocytes. Monocyte and innate-like activated T cell populations expressing interferon-stimulated genes (ISGs) increased 1 day post-vaccination with appearance of distinct subtype of ISG-activated cells, returning to baseline by day 14. Pre-treatment with oral corticosteroids effectively curtailed these ISG-associated inflammatory responses by decreasing chromatin accessibility of major ISGs, without hampering vaccine immunogenicity. Our findings provide insights into the human immune response following ChAd-based vaccination and propose a method to reduce inflammatory side effects.
Project description:Vector-based SARS-CoV-2 vaccines such as AstraZeneca's ChAdOx1 nCoV-19 have been associated with vaccine-induced thrombosis (TTS/VITT). We studied ChAdOx1 nCov-19 (AstraZeneca) and Ad26.COV2.S (Johnson & Johnson) and compared the vaccines using proteomics with mass spectrometric measurements. We could demonstrate that ChAdOx1 nCoV-19 contained significant amounts of human proteins in addition to adenoviral proteins. This was not the case for Ad26.COV2.S. Among the detected human proteins, proteasome subunits beta 1/delta and beta 5/MB1 were identified. In summary, both studied SARS-CoV-2 vaccines are markedly different concerning their content of contaminating proteins, which is most likely a determining factor for different frequencies of TTS/VITT after their application.
Project description:Objectives: To investigate the differences in efficacy and safety between the vector vaccine ChAdOx1 nCoV-19/AZD1222 (Oxford-AstraZeneca) and mRNA-based vaccine mRNA-1273 (Moderna), and evaluate the impact of anti-rheumatic medications on immunogenicity in patients with autoimmune rheumatic diseases (AIRD). Methods: From September 16 to November 15, 2021, we consecutively enrolled participants aged≥20 years with AIRD who received COVID-19 vaccination. The level of serum IgG antibodies to the SARS-Cov-2 receptor-binding domain on the spike protein S1 subunit was quantified by electrochemiluminescence immunoassay at 4-6 weeks after vaccination. The immunogenicity and adverse reactions between ChAdOx1 nCov-19/AZD1222 and mRNA-1273 were compared. Results: Of the 243 rheumatic disease patients who received COVID-19 vaccines, 113 and 130 were immunized with AZD1222 and mRNA-1273, respectively. The anti-SARS-CoV-2 IgG seropositivity rate was 78.8% (89/113) for AZD1222 and 83.1% (108/130) for mRNA-1273. The level of anti-SARS-Cov-2 IgG was higher in patients who received mRNA-1273 than in those who received AZD1222. Prednisolone-equivalent dose >5 mg/day, methotrexate (MTX), non-anti-tumor necrosis factor (TNF)-a biologics, and Janus kinase (JAK) inhibitor use were associated with inferior immunogenicity. All reported adverse reactions were minor. More localized pain at the injection site and less fever and chills were observed in patients receiving mRNA-1273 compared with those receiving AZD1222. Rheumatic disease activities after vaccination remained stable in most patients. Conclusions: mRNA-1273 and AZD1222 vaccines exhibited differential immunogenicity and adverse reaction profiles. Our study findings support temporary discontinuation of daily prednisolone dose >5 mg, MTX, non-anti-TNF-a biologics, or JAK inhibitors after COVID-19 vaccination.
Project description:Site-specific glycosylation analysis of the ChAdOx1 nCoV-19 derived Spike protein. Raw files for both the cleaved (S1/S2) and uncleaved (S0) protein are included.