Li, Chris Ka-fai, Wu, Hao, Yan, Huiping, Ma, Shiwu, Wang, Lili, Zhang, Mingxia, Tang, Xiaoping, Temperton, Nigel J. ORCID: https://orcid.org/0000-0002-7978-3815, Weiss, Robin A., Brenchley, Jason M., Douek, Daniel C., Mongkolsapaya, Juthathip, Tran, Bac-Hai, Lin, Chen-lung Steve, Screaton, Gavin R., Hou, Jin-lin, McMichael, Andrew J. and Xu, Xiao-Ning (2008) T Cell responses to whole SARS Coronavirus in humans. The Journal of Immunology, 181 (8). pp. 5490-5500. ISSN 0022-1767 (Print), 1550-6606 (Online) (doi:10.4049/jimmunol.181.8.5490)

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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-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 < 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
Additional Information:	[1] The online version of this article contains supplemental data.
Uncontrolled Keywords:	SARS, severe acute respiratory syndrome, CoV, coronaviru, PBMC, peripheral blood mononuclear cell, ICS, intracellular cytokine staining, SFC, spot forming cell, Nab, neutralizing Ab
Subjects:	R Medicine > RA Public aspects of medicine > RA0421 Public health. Hygiene. Preventive Medicine R Medicine > RC Internal medicine R Medicine > RZ Other systems of medicine
Faculty / School / Research Centre / Research Group:	Faculty of Engineering & Science > Medway School of Pharmacy Faculty of Engineering & Science
Related URLs:	Publisher
Last Modified:	27 Jul 2015 14:57
URI:	http://gala.gre.ac.uk/id/eprint/8558

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