T cell responses to whole SARS coronavirus in humans

J Immunol. 2008 Oct 15;181(8):5490-500. doi: 10.4049/jimmunol.181.8.5490.

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.

Publication types

  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Antibodies, Viral / immunology*
  • CD8-Positive T-Lymphocytes / immunology*
  • Cohort Studies
  • Cytokines / immunology
  • Female
  • Humans
  • Immunologic Memory*
  • Leukocyte Common Antigens / immunology
  • Lysosomal-Associated Membrane Protein 1 / immunology
  • Male
  • Middle Aged
  • Proteome / immunology
  • SARS Virus / immunology*
  • Severe Acute Respiratory Syndrome / immunology*
  • Severe Acute Respiratory Syndrome / mortality
  • Th2 Cells / immunology*
  • Tumor Necrosis Factor Receptor Superfamily, Member 7 / immunology
  • Viral Vaccines / immunology

Substances

  • Antibodies, Viral
  • Cytokines
  • Lysosomal-Associated Membrane Protein 1
  • Proteome
  • Tumor Necrosis Factor Receptor Superfamily, Member 7
  • Viral Vaccines
  • Leukocyte Common Antigens