The prospect of universal coronavirus immunity: characterization of reciprocal and non-reciprocal T cell responses against SARS-CoV2 and common human coronaviruses

Frontiers in Immunology

Immunology

Jianing Fu¹  Prabesh Khatiwada¹  Pawel J. Muranski¹  Edoardo Migliori¹  Markus Y. Mapara¹  Megan Sykes¹  Mithil K. Soni¹  Hei Ton Chan²  Michael S. May²  Rodica Ciubotariu²  Jian Pan²  Amer Assal³  Marcus R. Pereira⁴  Valeria De Giorgi⁵ 

[1] Columbia Center for Translational Immunology, Department of Medicine, Columbia University, New York, NY, United States;Columbia University Medical Center, Herbert Irving Comprehensive Cancer Center, New York, NY, United States;Department of Medicine, Blood and Marrow Transplantation and Cell Therapy Program, Columbia University Irving Medical Center, New York, NY, United States;Columbia University Medical Center, Herbert Irving Comprehensive Cancer Center, New York, NY, United States;Department of Medicine, Division of Infectious Disease, Columbia University College of Physicians and Surgeons, New York, NY, United States;Department of Transfusion Medicine, National Institutes of Health Clinical Center, Bethesda, MD, United States;

关键词: SARS-CoV-2;    human coronavirus;    omicron;    multicoronavirus-specific T cells;    cross-reactive T cells;    SARS-CoV-2 variants;   

DOI  :  10.3389/fimmu.2023.1212203

 received in 2023-04-25, accepted in 2023-09-25,  发布年份 2023

来源: Frontiers

【 摘 要 】

T cell immunity plays a central role in clinical outcomes of Coronavirus Infectious Disease 2019 (COVID-19) and T cell-focused vaccination or cellular immunotherapy might provide enhanced protection for some immunocompromised patients. Pre-existing T cell memory recognizing SARS-CoV-2 antigens antedating COVID-19 infection or vaccination, may have developed as an imprint of prior infections with endemic non-SARS human coronaviruses (hCoVs) OC43, HKU1, 229E, NL63, pathogens of “common cold”. In turn, SARS-CoV-2-primed T cells may recognize emerging variants or other hCoV viruses and modulate the course of subsequent hCoV infections. Cross-immunity between hCoVs and SARS-CoV-2 has not been well characterized. Here, we systematically investigated T cell responses against the immunodominant SARS-CoV-2 spike, nucleocapsid and membrane proteins and corresponding antigens from α- and β-hCoVs among vaccinated, convalescent, and unexposed subjects. Broad T cell immunity against all tested SARS-CoV-2 antigens emerged in COVID-19 survivors. In convalescent and in vaccinated individuals, SARS-CoV-2 spike-specific T cells reliably recognized most SARS-CoV-2 variants, however cross-reactivity against the omicron variant was reduced by approximately 47%. Responses against spike, nucleocapsid and membrane antigens from endemic hCoVs were significantly more extensive in COVID-19 survivors than in unexposed subjects and displayed cross-reactivity between α- and β-hCoVs. In some, non-SARS hCoV-specific T cells demonstrated a prominent non-reciprocal cross-reactivity with SARS-CoV-2 antigens, whereas a distinct anti-SARS-CoV-2 immunological repertoire emerged post-COVID-19, with relatively limited cross-recognition of non-SARS hCoVs. Based on this cross-reactivity pattern, we established a strategy for in-vitro expansion of universal anti-hCoV T cells for adoptive immunotherapy. Overall, these results have implications for the future design of universal vaccines and cell-based immune therapies against SARS- and non-SARS-CoVs.

【 授权许可】

Unknown   
Copyright © 2023 Soni, Migliori, Fu, Assal, Chan, Pan, Khatiwada, Ciubotariu, May, Pereira, De Giorgi, Sykes, Mapara and Muranski