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| Article Authors: | Chris Ka-fai Li; Hao Wu; Huiping Yan; Shiwu Ma; Lili Wang; Mingxia Zhang; Xiaoping Tang; Nigel J Temperton; Robin A Weiss; Jason M Brenchley; Daniel C Douek; Juthathip Mongkolsapaya; Bac-Hai Tran; Chen-lung Steve Lin; Gavin R Screaton; Jin-lin Hou; Andrew J McMichael; Xiao-Ning Xu |
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| Article Title: | T cell responses to whole SARS coronavirus in humans. |
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| Reference ID: | 1013720 |
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| Abstract: | Effective vaccines should confer long-term protection against future outbreaks of severe acute respiratory syndrome (SARS) caused by a novel zoonotic coronavirus (SARS-CoV) with unknown animal reservoirs. We conducted a cohort study examining multiple parameters of immune responses to SARS-CoV infection, aiming to identify the immune correlates of protection. We used a matrix of overlapping peptides spanning whole SARS-CoV proteome to determine T cell responses from 128 SARS convalescent samples by ex vivo IFN-gamma ELISPOT assays. Approximately 50% of convalescent SARS patients were positive for T cell responses, and 90% possessed strongly neutralizing Abs. Fifty-five novel T cell epitopes were identified, with spike protein dominating total T cell responses. CD8(+) T cell responses were more frequent and of a greater magnitude than CD4(+) T cell responses (p < 0.001). Polychromatic cytometry analysis indicated that the virus-specific T cells from the severe group tended to be a central memory phenotype (CD27(+)/CD45RO(+)) with a significantly higher frequency of polyfunctional CD4(+) T cells producing IFN-gamma, TNF-alpha, and IL-2, and CD8(+) T cells producing IFN-gamma, TNF-alpha, and CD107a (degranulation), as compared with the mild-moderate group. Strong T cell responses correlated significantly (p < 0.05) with higher neutralizing Ab. The serum cytokine profile during acute infection indicated a significant elevation of innate immune responses. Increased Th2 cytokines were observed in patients with fatal infection. Our study provides a roadmap for the immunogenicity of SARS-CoV and types of immune responses that may be responsible for the virus clearance, and should serve as a benchmark for SARS-CoV vaccine design and evaluation. |
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| Affiliations: | MRC Human Immunology Unit, Weatherall Institute of Molecular Medicine, University of Oxford, Oxford, UK. |
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| Date: | 2008 |
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| Reference Type: | Literature |
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| PubMed ID: | 18832706 |
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| Journal: | J Immunol |
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| Journal Volume: | 181 |
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| Article Pages: | 5490-500 |
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| Journal ISSN: | 1550-6606 |
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| Article Chemical List: | Antibodies, Viral;Antigens, CD27;Cytokines;Lysosomal-Associated Membrane Protein 1;Proteome;Viral Vaccines;Antigens, CD45 |
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| Article MeSH List: | Adult; Antibodies, Viral(immunology); Antigens, CD27(immunology); Antigens, CD45(immunology); CD8-Positive T-Lymphocytes(immunology); Cohort Studies; Cytokines(immunology); Female; Humans; Immunologic Memory; Lysosomal-Associated Membrane Protein 1(immunology); Male; Middle Aged; Proteome(immunology); SARS Virus(immunology); Severe Acute Respiratory Syndrome(immunology; mortality); Th2 Cells(immunology); Viral Vaccines(immunology) |
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| Curation Last Updated: | 2013-05-28 21:35:01 |
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