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Eser, T.M.* ; Baranov, O.* ; Huth, M. ; Ahmed, M.I.M.* ; Deák, F.* ; Held, K.* ; Lin, L.* ; Pekayvaz, K.* ; Leunig, A.* ; Nicolai, L.* ; Pollakis, G.* ; Buggert, M.* ; Price, D.A.* ; Rubio-Acero, R.* ; Reich, J.* ; Falk, P.* ; Markgraf, A.* ; Puchinger, K.* ; Castelletti, N.* ; Olbrich, L.* ; Vanshylla, K.* ; Klein, F.* ; Wieser, A.* ; Hasenauer, J. ; Kroidl, I.* ; Hoelscher, M.* ; Geldmacher, C.*

Nucleocapsid-specific T cell responses associate with control of SARS-CoV-2 in the upper airways before seroconversion.

Nat. Commun. 14:2952 (2023)
Postprint Publ. Version/Full Text DOI PMC
Open Access Gold
Creative Commons Lizenzvertrag
Despite intensive research since the emergence of SARS-CoV-2, it has remained unclear precisely which components of the early immune response protect against the development of severe COVID-19. Here, we perform a comprehensive immunogenetic and virologic analysis of nasopharyngeal and peripheral blood samples obtained during the acute phase of infection with SARS-CoV-2. We find that soluble and transcriptional markers of systemic inflammation peak during the first week after symptom onset and correlate directly with upper airways viral loads (UA-VLs), whereas the contemporaneous frequencies of circulating viral nucleocapsid (NC)-specific CD4+ and CD8+ T cells correlate inversely with various inflammatory markers and UA-VLs. In addition, we show that high frequencies of activated CD4+ and CD8+ T cells are present in acutely infected nasopharyngeal tissue, many of which express genes encoding various effector molecules, such as cytotoxic proteins and IFN-γ. The presence of IFNG mRNA-expressing CD4+ and CD8+ T cells in the infected epithelium is further linked with common patterns of gene expression among virus-susceptible target cells and better local control of SARS-CoV-2. Collectively, these results identify an immune correlate of protection against SARS-CoV-2, which could inform the development of more effective vaccines to combat the acute and chronic illnesses attributable to COVID-19.
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Publication type Article: Journal article
Document type Scientific Article
Keywords Virus; Infection; Proteins; Immunity; Hiv
Language english
Publication Year 2023
HGF-reported in Year 2023
ISSN (print) / ISBN 2041-1723
e-ISSN 2041-1723
Journal Nature Communications
Quellenangaben Volume: 14, Issue: 1, Pages: , Article Number: 2952 Supplement: ,
Publisher Nature Publishing Group
Publishing Place London
Reviewing status Peer reviewed
Institute(s) Institute of Computational Biology (ICB)
POF-Topic(s) 30205 - Bioengineering and Digital Health
Research field(s) Enabling and Novel Technologies
PSP Element(s) G-503800-010
G-553800-001
Grants National Institutes of Health Research (NIHR)

National Institute for Health Research
Ministry for Education and Research
Deutsche Forschungsgemeinschaft
Bavarian State Ministry of Science and the Arts
DOI 10.1038/s41467-023-38020-8
WOS ID 001001099700008
Scopus ID 85160117134
PubMed ID 37225706
Erfassungsdatum 2023-10-06
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