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

69 Scopus citations

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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