T Cell Responses to Whole SARS Coronavirus in Humans

作者：Chris Ka‐fai Li, Hao Wu, Huiping Yan, Shiwu Ma, Lili Wang, Mingxia Zhang, Xiaoping Tang, Nigel Temperton, Robin A. Weiss, Jason M. Brenchley, Daniel C. Douek, Juthathip Mongkolsapaya, Bac-Hai Tran, Chen-Lung Steve Lin, Gavin Screaton, Jin-Lin Hou, Andrew J. McMichael, Xiao-Ning Xu · 发表于：The Journal of Immunology · 年份：2008 · DOI：10.4049/jimmunol.181.8.5490 · 被引用次数：541 · 研究领域：SARS-CoV-2 and COVID-19 Research、vaccines and immunoinformatics approaches、Influenza Virus Research Studies

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 w...