COVID-19: コアタンパク質を標的とする免疫細胞は、初期の免疫防御に重要である(COVID-19: Immune cells targeting core protein are important for early immune defense)


2023-05-24 ミュンヘン大学(LMU)



ヌクレオカプシド特異的T細胞応答が血清変換前の上気道におけるSARS-CoV-2の制御と関連することがわかった Nucleocapsid-specific T cell responses associate with control of SARS-CoV-2 in the upper airways before seroconversion

Tabea M. Eser,Olga Baranov,Manuel Huth,Mohammed I. M. Ahmed,Flora Deák,Kathrin Held,Luming Lin,Kami Pekayvaz,Alexander Leunig,Leo Nicolai,Georgios Pollakis,Marcus Buggert,David A. Price,Raquel Rubio-Acero,Jakob Reich,Philine Falk,Alissa Markgraf,Kerstin Puchinger,Noemi Castelletti,Laura Olbrich,Kanika Vanshylla,Florian Klein,Andreas Wieser,Jan Hasenauer,Inge Kroidl,Michael Hoelscher & Christof Geldmacher
Nature Communications  Published:24 May 2023

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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.