Identification of murine CD8 T cell epitopes in codon-optimized SARS-associated coronavirus spike protein

Yan Zhi, Gary P. Kobinger, Heather Jordan, Katie Suchma, Susan R. Weiss, Hao Shen, Gregory Schumer, Guangping Gao, Julie L. Boyer, Ronald G. Crystal, James M. Wilson

Research output: Contribution to journalArticlepeer-review

Abstract

The causative agent of severe acute respiratory syndrome (SARS) has been identified as a new type of coronavirus, SARS-associated coronavirus (SARS-CoV). CD8 T cells play an important role in controlling diseases caused by other coronaviruses and in mediating vaccine-induced protective immunity in corresponding animal models. The spike protein, a main surface antigen of SARS-CoV, is one of the most important antigen candidates for vaccine design. Overlapping peptides were used to identify major histocompatibility complex class I-restricted epitopes in mice immunized with vectors encoding codon-optimized SARS-CoV spike protein. CD8 T-cell responses were mapped to two H-2b-restricted epitopes (S436-443 and S525-532) and one H-2 d-restricted epitope (S366-374). The identification of these epitopes will facilitate the evaluation of vaccine strategies in murine models of SARS-CoV infection. Furthermore, codon and promoter optimizations can greatly enhance the overall immunogenicity of spike protein in the context of replication-defective human and simian adenoviral vaccine carriers. The optimized recombinant adenoviral vaccine vectors encoding spike can generate robust antigen-specific cellular immunity in mice and may potentially be useful for control of SARS-CoV infection.

Original languageEnglish (US)
Pages (from-to)34-45
Number of pages12
JournalVirology
Volume335
Issue number1
DOIs
StatePublished - Apr 25 2005
Externally publishedYes

Keywords

  • CD8 T cells
  • Codon optimization
  • MHC class I epitope
  • Promoter optimization
  • Replication-defective adenoviral vaccine vectors
  • SARS-CoV

ASJC Scopus subject areas

  • Virology

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