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

Virology. 2005 Apr 25;335(1):34-45. doi: 10.1016/j.virol.2005.01.050.

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-2(b)-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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenoviruses, Human / genetics
  • Adenoviruses, Human / immunology
  • Adenoviruses, Human / metabolism
  • Amino Acid Sequence
  • Animals
  • CD8-Positive T-Lymphocytes / immunology*
  • Cell Line
  • Chlorocebus aethiops
  • Codon
  • Epitope Mapping*
  • Epitopes, T-Lymphocyte / immunology*
  • Genetic Vectors / administration & dosage
  • Genetic Vectors / immunology
  • H-2 Antigens / metabolism
  • Histocompatibility Antigen H-2D
  • Humans
  • Immunization
  • Membrane Glycoproteins / genetics
  • Membrane Glycoproteins / immunology*
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • Molecular Sequence Data
  • Peptides / chemistry
  • Peptides / immunology
  • SARS Virus / immunology*
  • Severe Acute Respiratory Syndrome / prevention & control
  • Spike Glycoprotein, Coronavirus
  • Vero Cells
  • Viral Envelope Proteins / genetics
  • Viral Envelope Proteins / immunology*
  • Viral Vaccines / administration & dosage
  • Viral Vaccines / immunology

Substances

  • Codon
  • Epitopes, T-Lymphocyte
  • H-2 Antigens
  • Histocompatibility Antigen H-2D
  • Membrane Glycoproteins
  • Peptides
  • Spike Glycoprotein, Coronavirus
  • Viral Envelope Proteins
  • Viral Vaccines