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https://hdl.handle.net/2440/65849
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Type: | Journal article |
Title: | T Cell Responses to Whole SARS Coronavirus in Humans |
Author: | Li, C. Wu, H. Yan, H. Ma, S. Wang, L. Zhang, M. Tang, X. Temperton, N. Weiss, R. Brenchley, J. Douek, D. Mongkolsapaya, J. Tran, H. Lin, C.L. Screaton, G. Hou, J. McMichael, A. Xu, X. |
Citation: | Journal of Immunology, 2008; 181(8):5490-5500 |
Publisher: | Amer Assoc Immunologists |
Issue Date: | 2008 |
ISSN: | 0022-1767 1550-6606 |
Statement of Responsibility: | 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, and Xiao-Ning Xu |
Abstract: | <jats:title>Abstract</jats:title> <jats:p>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 &lt; 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-α, 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 &lt; 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.</jats:p> |
Rights: | Copyright ©2008 by The American Association of Immunologists, Inc. All rights reserved. |
DOI: | 10.4049/jimmunol.181.8.5490 |
Description (link): | http://www.jimmunol.org/content/181/8/5490.abstract |
Published version: | http://dx.doi.org/10.4049/jimmunol.181.8.5490 |
Appears in Collections: | Aurora harvest Medicine publications |
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