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The SARS-CoV-2 T-cell immunity is directed against the spike, membrane, and nucleocapsid protein and associated with COVID 19 severity [article]

Constantin J Thieme, Moritz Anft, Krystallenia Paniskaki, Arturo Blazquez-Navarro, Adrian Doevelaar, Felix S Seibert, Bodo Hoelzer, Margarethe Justine Konik, Thorsten Brenner, Clemens Tempfer, Carsten Watzl, Sebastian Dolff (+6 others)
2020 medRxiv   pre-print

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https://web.archive.org/web/20200729151927/https://www.medrxiv.org/content/medrxiv/early/2020/05/16/2020.05.13.20100636.full.pdf

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Identification of immunogenic targets of SARS-CoV-2 is crucial for monitoring of antiviral immunity and vaccine design. Currently, mainly anti-spike (S)-protein adaptive immunity is investigated. However, also the nucleocapsid (N)- and membrane (M)-proteins should be considered as diagnostic and prophylactic targets. The aim of our study was to explore and compare the immunogenicity of SARS-CoV-2 S-, M- and N-proteins in context of different COVID-19 manifestations. Analyzing a cohort of
more » ... 9 patients with moderate, severe, and critical disease severity, we show that overlapping peptide pools (OPP) of all three proteins can activate SARS-CoV-2-reactive T-cells with a stronger response of CD4+ compared to CD8+ T-cells. Although interindividual variations for the three proteins were observed, M protein induced the highest frequencies of CD4+ T-cells, suggesting its relevance as diagnostic and vaccination target. Importantly, patients with critical COVID-19 demonstrated the strongest T-cell response, including the highest frequencies of cytokine-producing bi- and trifunctional T-cells, for all three proteins. Although the higher magnitude and superior functionality of SARS-CoV-2-reactive T-cells in critical patients can also be a result of a stronger immunogenicity provided by severe infection, it disproves the hypothesis of insufficient SARS-CoV-2-reactive immunity in critical COVID-19. To this end, activation of effector T-cells with differentiated memory phenotype found in our study could cause hyper-reactive response in critical cases leading to immunopathogenesis. Conclusively, since the S-, M-, and N-proteins induce T-cell responses with individual differences, all three proteins should be evaluated for diagnostics and therapeutic strategies to avoid underestimation of cellular immunity and to deepen our understanding of COVID-19 immunity.
doi:10.1101/2020.05.13.20100636 fatcat:6fb2ub7ocbcghafpdtsawi4tlq
Citation

Constantin J Thieme, Moritz Anft, Krystallenia Paniskaki, Arturo Blazquez-Navarro, Adrian Doevelaar, Felix S Seibert, Bodo Hoelzer, Margarethe Justine Konik, Thorsten Brenner, Clemens Tempfer, Carsten Watzl, Sebastian Dolff, Ulf Dittmer, Timm H. Westhoff, Oliver Witzke, Ulrik Stervbo, Toralf Roch, Nina Babel. "The SARS-CoV-2 T-cell immunity is directed against the spike, membrane, and nucleocapsid protein and associated with COVID 19 severity." medRxiv (2020)