دورية أكاديمية
High frequencies of alpha common cold coronavirus/SARS-CoV-2 cross-reactive functional CD4 + and CD8 + memory T cells are associated with protection from symptomatic and fatal SARS-CoV-2 infections in unvaccinated COVID-19 patients.
| العنوان: | High frequencies of alpha common cold coronavirus/SARS-CoV-2 cross-reactive functional CD4 + and CD8 + memory T cells are associated with protection from symptomatic and fatal SARS-CoV-2 infections in unvaccinated COVID-19 patients. |
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| المؤلفون: | Coulon PG; Laboratory of Cellular and Molecular Immunology, Gavin Herbert Eye Institute, University of California Irvine, School of Medicine, Irvine, CA, United States., Prakash S; Laboratory of Cellular and Molecular Immunology, Gavin Herbert Eye Institute, University of California Irvine, School of Medicine, Irvine, CA, United States., Dhanushkodi NR; Laboratory of Cellular and Molecular Immunology, Gavin Herbert Eye Institute, University of California Irvine, School of Medicine, Irvine, CA, United States., Srivastava R; Laboratory of Cellular and Molecular Immunology, Gavin Herbert Eye Institute, University of California Irvine, School of Medicine, Irvine, CA, United States., Zayou L; Laboratory of Cellular and Molecular Immunology, Gavin Herbert Eye Institute, University of California Irvine, School of Medicine, Irvine, CA, United States., Tifrea DF; Department of Pathology and Laboratory Medicine, School of Medicine, University of California Irvine, Irvine, CA, United States., Edwards RA; Department of Pathology and Laboratory Medicine, School of Medicine, University of California Irvine, Irvine, CA, United States., Figueroa CJ; Department of Surgery, Divisions of Trauma, Burns and Critical Care, School of Medicine, University of California Irvine, Irvine, CA, United States., Schubl SD; Department of Surgery, Divisions of Trauma, Burns and Critical Care, School of Medicine, University of California Irvine, Irvine, CA, United States., Hsieh L; Department of Medicine, Division of Infectious Diseases and Hospitalist Program, School of Medicine, University of California Irvine, Irvine, CA, United States., Nesburn AB; Laboratory of Cellular and Molecular Immunology, Gavin Herbert Eye Institute, University of California Irvine, School of Medicine, Irvine, CA, United States., Kuppermann BD; Laboratory of Cellular and Molecular Immunology, Gavin Herbert Eye Institute, University of California Irvine, School of Medicine, Irvine, CA, United States., Bahraoui E; Université Paul Sabatier, Infinity, Inserm, Toulouse, France., Vahed H; Department of Vaccines and Immunotherapies, TechImmune, LLC, University Lab Partners, Irvine, CA, United States., Gil D; Department of Vaccines and Immunotherapies, TechImmune, LLC, University Lab Partners, Irvine, CA, United States., Jones TM; Department of Vaccines and Immunotherapies, TechImmune, LLC, University Lab Partners, Irvine, CA, United States., Ulmer JB; Department of Vaccines and Immunotherapies, TechImmune, LLC, University Lab Partners, Irvine, CA, United States., BenMohamed L; Laboratory of Cellular and Molecular Immunology, Gavin Herbert Eye Institute, University of California Irvine, School of Medicine, Irvine, CA, United States.; Université Paul Sabatier, Infinity, Inserm, Toulouse, France.; Department of Vaccines and Immunotherapies, TechImmune, LLC, University Lab Partners, Irvine, CA, United States.; Institute for Immunology, The University of California Irvine, School of Medicine, Irvine, CA, United States. |
| المصدر: | Frontiers in immunology [Front Immunol] 2024 Mar 28; Vol. 15, pp. 1343716. Date of Electronic Publication: 2024 Mar 28 (Print Publication: 2024). |
| نوع المنشور: | Journal Article; Research Support, U.S. Gov't, P.H.S. |
| اللغة: | English |
| بيانات الدورية: | Publisher: Frontiers Research Foundation] Country of Publication: Switzerland NLM ID: 101560960 Publication Model: eCollection Cited Medium: Internet ISSN: 1664-3224 (Electronic) Linking ISSN: 16643224 NLM ISO Abbreviation: Front Immunol Subsets: MEDLINE |
| أسماء مطبوعة: | Original Publication: [Lausanne : Frontiers Research Foundation] |
| مواضيع طبية MeSH: | COVID-19* , Common Cold*, Humans ; SARS-CoV-2 ; CTLA-4 Antigen ; CD8-Positive T-Lymphocytes ; Memory T Cells ; Hepatitis A Virus Cellular Receptor 2 ; Programmed Cell Death 1 Receptor ; CD4-Positive T-Lymphocytes ; Epitopes |
| مستخلص: | Background: Cross-reactive SARS-CoV-2-specific memory CD4 + and CD8 + T cells are present in up to 50% of unexposed, pre-pandemic, healthy individuals (UPPHIs). However, the characteristics of cross-reactive memory CD4 + and CD8 + T cells associated with subsequent protection of asymptomatic coronavirus disease 2019 (COVID-19) patients (i.e., unvaccinated individuals who never develop any COVID-19 symptoms despite being infected with SARS-CoV-2) remains to be fully elucidated. Methods: This study compares the antigen specificity, frequency, phenotype, and function of cross-reactive memory CD4 + and CD8 + T cells between common cold coronaviruses (CCCs) and SARS-CoV-2. T-cell responses against genome-wide conserved epitopes were studied early in the disease course in a cohort of 147 unvaccinated COVID-19 patients who were divided into six groups based on the severity of their symptoms. Results: Compared to severely ill COVID-19 patients and patients with fatal COVID-19 outcomes, the asymptomatic COVID-19 patients displayed significantly: (i) higher rates of co-infection with the 229E alpha species of CCCs (α-CCC-229E); (ii) higher frequencies of cross-reactive functional CD134 + CD137 + CD4 + and CD134 + CD137 + CD8 + T cells that cross-recognized conserved epitopes from α-CCCs and SARS-CoV-2 structural, non-structural, and accessory proteins; and (iii) lower frequencies of CCCs/SARS-CoV-2 cross-reactive exhausted PD-1 + TIM3 + TIGIT + CTLA4 + CD4 + and PD-1 + TIM3 + TIGIT + CTLA4 + CD8 + T cells, detected both ex vivo and in vitro . Conclusions: These findings (i) support a crucial role of functional, poly-antigenic α-CCCs/SARS-CoV-2 cross-reactive memory CD4 + and CD8 + T cells, induced following previous CCCs seasonal exposures, in protection against subsequent severe COVID-19 disease and (ii) provide critical insights into developing broadly protective, multi-antigen, CD4 + , and CD8 + T-cell-based, universal pan-Coronavirus vaccines capable of conferring cross-species protection. Competing Interests: Authors HV, DG, TJ and JU were employed by company TechImmune LLC. LB has an equity interest in TechImmune, LLC., a company that may potentially benefit from the research results and serves on the company’s Scientific Advisory Board. LB’s relationship with TechImmune, LLC., has been reviewed and approved by the University of California, Irvine by its conflict-of-interest policies. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision. (Copyright © 2024 Coulon, Prakash, Dhanushkodi, Srivastava, Zayou, Tifrea, Edwards, Figueroa, Schubl, Hsieh, Nesburn, Kuppermann, Bahraoui, Vahed, Gil, Jones, Ulmer and BenMohamed.) |
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| معلومات مُعتمدة: | R41 AI138764 United States AI NIAID NIH HHS; R01 AI143348 United States AI NIAID NIH HHS; R43 AI174383 United States AI NIAID NIH HHS; R01 AI158060 United States AI NIAID NIH HHS; R43 AI124911 United States AI NIAID NIH HHS; R01 AI150091 United States AI NIAID NIH HHS; R21 AI143326 United States AI NIAID NIH HHS; R21 AI110902 United States AI NIAID NIH HHS; R21 AI147499 United States AI NIAID NIH HHS |
| فهرسة مساهمة: | Keywords: SARS-CoV-2; CD4 + T cells; CD8 + T cells; COVID-19; asymptomatic; common cold coronavirus; exhaustion α-CCCs/SARS-CoV-2 cross-reactive T cells in asymptomatic COVID-19 infection; symptomatic |
| المشرفين على المادة: | 0 (CTLA-4 Antigen) 0 (Hepatitis A Virus Cellular Receptor 2) 0 (Programmed Cell Death 1 Receptor) 0 (Epitopes) |
| تواريخ الأحداث: | Date Created: 20240412 Date Completed: 20240415 Latest Revision: 20240425 |
| رمز التحديث: | 20240425 |
| مُعرف محوري في PubMed: | PMC11007208 |
| DOI: | 10.3389/fimmu.2024.1343716 |
| PMID: | 38605956 |
| قاعدة البيانات: | MEDLINE |
Full Text Finder | تدمد: | 1664-3224 |
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| DOI: | 10.3389/fimmu.2024.1343716 |