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Discrete immune response signature to SARS-CoV-2 mRNA vaccination versus infection

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  • Discrete immune response signature to SARS-CoV-2 mRNA vaccination versus infection
    Discrete immune response signature to SARS-CoV-2 mRNA vaccination versus infection

    Ellie N. Ivanova, Joseph C. Devlin, Terkild B. Buus, Akiko Koide, Amber Cornelius, Marie I. Samanovic, Alberto Herrera, Chenzhen Zhang, Ludovic Desvignes, Niels Odum, Robert Ulrich, Mark J. Mulligan, Shohei Koide, Kelly V. Ruggles, Ramin S. Herati, Sergei B. Koralov
    medRxiv 2021.04.20.21255677; doi: This article is a preprint and has not been peer-reviewed [what does this mean?]. It reports new medical research that has yet to be evaluated and so should not be used to guide clinical practice.


    Both SARS-CoV-2 infection and vaccination elicit potent immune responses. A number of studies have described immune responses to SARS-CoV-2 infection. However, beyond antibody production, immune responses to COVID-19 vaccines remain largely uncharacterized. Here, we performed multimodal single-cell sequencing on peripheral blood of patients with acute COVID-19 and healthy volunteers before and after receiving the SARS-CoV-2 BNT162b2 mRNA vaccine to compare the immune responses elicited by the virus and by this vaccine. Phenotypic and transcriptional profiling of immune cells, coupled with reconstruction of the B and T cell antigen receptor rearrangement of individual lymphocytes, enabled us to characterize and compare the host responses to the virus and to defined viral antigens. While both infection and vaccination induced robust innate and adaptive immune responses, our analysis revealed significant qualitative differences between the two types of immune challenges. In COVID-19 patients, immune responses were characterized by a highly augmented interferon response which was largely absent in vaccine recipients. Increased interferon signaling likely contributed to the observed dramatic upregulation of cytotoxic genes in the peripheral T cells and innate-like lymphocytes in patients but not in immunized subjects. Analysis of B and T cell receptor repertoires revealed that while the majority of clonal B and T cells in COVID-19 patients were effector cells, in vaccine recipients clonally expanded cells were primarily circulating memory cells. Importantly, the divergence in immune subsets engaged, the transcriptional differences in key immune populations, and the differences in maturation of adaptive immune cells revealed by our analysis have far-ranging implications for immunity to this novel pathogen.


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