T cell responses to whole SARS coronavirus in humans

Li, C.K.F. and Wu, H. and Yan, H. and Ma, S. and Wang, L. and Zhang, M. and Tang, X. and Temperton, N.J. and Weiss, R.A. and Brenchley, J.M. and Douek, D.C. and Mongkolsapaya, J. and Tran, B.H. and Lin, C.L.S. and Screaton, G.R. and Hou, J.L. and McMichael, A.J. and Xu, X.N. (2008) T cell responses to whole SARS coronavirus in humans. Journal of Immunology, 181 (8). pp. 5490-5500. ISSN 0022-1767. (Full text available)

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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-γ 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-γ, TNF-γ, and IL-2, and CD8+ T cells producing IFN-γ, TNF-α, 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.

Item Type: Article
Uncontrolled keywords: CD27 antigen, CD45RO antigen, epitope, gamma interferon, interleukin 2, lysosome associated membrane protein 1, neutralizing antibody, peptide, proteome, severe acute respiratory syndrome vaccine, tumor necrosis factor alpha, CD45 antigen, cytokine, virus antibody, virus vaccine, adult, article, CD4+ T lymphocyte, CD8+ T lymphocyte, cellular immunity, cohort analysis, controlled study, convalescence, cytokine production, cytometry, degranulation, enzyme linked immunospot assay, ex vivo study, female, human, human cell, immune response, immunity, immunogenicity, innate immunity, major clinical study, male, nucleotide sequence, phenotype, priority journal, SARS coronavirus, severe acute respiratory syndrome, T lymphocyte, Th2 cell, clinical trial, immunological memory, immunology, middle aged, mortality, multicenter study, Adult, Antibodies, Viral, Antigens, CD27, Antigens, CD45, CD8-Positive T-Lymphocytes, Cohort Studies, Cytokines, Female, Humans, Immunologic Memory, Lysosomal-Associated Membrane Protein 1, Male, Middle Aged, Proteome, SARS Virus, Severe Acute Respiratory Syndrome, Th2 Cells, Viral Vaccines
Subjects: Q Science > QR Microbiology > QR355 Virology
Divisions: Faculties > Science Technology and Medical Studies > Medway School of Pharmacy
Depositing User: Nigel Temperton
Date Deposited: 02 Aug 2012 10:05
Last Modified: 10 Aug 2012 13:52
Resource URI: http://kar.kent.ac.uk/id/eprint/29994 (The current URI for this page, for reference purposes)
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