나일강 (Universitatsmedizin Charite)

한빛사논문

조회265

Universitatsmedizin Charite

J. Med. Virol., Mar 2024, 96 (3) | https://doi.org/10.1002/jmv.29539 Comparable CD8+ T-cell responses to SARS-CoV-2 vaccination in single-cell transcriptomics of recently allogeneic transplanted patients and healthy individuals

Eva Tranter ¹, Marco Frentsch ^1,2, Marie Luise Hütter-Krönke ¹, Giang Lam Vuong ¹, David Busch ¹, Lucie Loyal ^3,4, Larissa Henze^3,4, Stanislav Rosnev ¹, Igor-Wolfgang Blau ¹, Andreas Thiel ^3,4, Dieter Beule ⁵, Lars Bullinger^1,6,7, Benedikt Obermayer ⁵, Il-Kang Na ^1,2,3,6,7

¹Medizinische Klinik m. S. Hämatologie, Onkologie und Tumorimmunologie, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, Charité-Universitätsmedizin Berlin, Berlin, Germany.

²BIH Center for Regenerative Therapies, Berlin Institute of Health at Charité Universitätsmedizin Berlin, Berlin, Germany.

³Si-M/"Der Simulierte Mensch", A Science Framework of Technische Universität Berlin and Charité-Universitätsmedizin Berlin, Berlin, Germany.

⁴BIH Center of Immunomics-Regenerative Immunology and Aging, Berlin Institute of Health at Charité-Universitätsmedizin Berlin, Berlin, Germany.

⁵Core Unit Bioinformatics, Berlin Institute of Health at Charité-Universitätsmedizin Berlin, Berlin, Germany.

⁶German Cancer Consortium (DKTK), Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Charité Universitätsmedizin Berlin, Berlin, Germany.

⁷ECRC Experimental and Clinical Research Center, Corporate Member of Freie Universität Berlin and Humboldt Universität zu Berlin, Charité Universitätsmedizin Berlin, Berlin, Germany.

Benedikt Obermayer and Il-Kang Na contributed equally to this study.

CORRESPONDING AUTHOR : Il-Kang Na

Abstract

Despite extensive research on severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination responses in healthy individuals, there is comparatively little known beyond antibody titers and T-cell responses in the vulnerable cohort of patients after allogeneic hematopoietic stem cell transplantation (ASCT). In this study, we assessed the serological response and performed longitudinal multimodal analyses including T-cell functionality and single-cell RNA sequencing combined with T cell receptor (TCR)/B cell receptor (BCR) profiling in the context of BNT162b2 vaccination in ASCT patients. In addition, these data were compared to publicly available data sets of healthy vaccinees. Protective antibody titers were achieved in 40% of patients. We identified a distorted B- and T-cell distribution, a reduced TCR diversity, and increased levels of exhaustion marker expression as possible causes for the poorer vaccine response rates in ASCT patients. Immunoglobulin heavy chain gene rearrangement after vaccination proved to be highly variable in ASCT patients. Changes in TCRα and TCRβ gene rearrangement after vaccination differed from patterns observed in healthy vaccinees. Crucially, ASCT patients elicited comparable proportions of SARS-CoV-2 vaccine-induced (VI) CD8 ⁺ T-cells, characterized by a distinct gene expression pattern that is associated with SARS-CoV-2 specificity in healthy individuals. Our study underlines the impaired immune system and thus the lower vaccine response rates in ASCT patients. However, since protective vaccine responses and VI CD8 ⁺ T-cells can be induced in part of ASCT patients, our data advocate early posttransplant vaccination due to the high risk of infection in this vulnerable group.

논문정보

형식Research article
게재일2024년 03월 (BRIC 등록일 2024-04-02)
연구진국외 연구진
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