Identification of immunodominant sites on the spike protein of severe acute respiratory syndrome (SARS) coronavirus: implication for developing SARS diagnostics and vaccines

J Immunol. 2004 Sep 15;173(6):4050-7. doi: 10.4049/jimmunol.173.6.4050.

Abstract

The spike (S) protein of severe acute respiratory syndrome (SARS) coronavirus (SARS-CoV) is not only responsible for receptor binding and virus fusion, but also a major Ag among the SARS-CoV proteins that induces protective Ab responses. In this study, we showed that the S protein of SARS-CoV is highly immunogenic during infection and immunizations, and contains five linear immunodominant sites (sites I to V) as determined by Pepscan analysis with a set of synthetic peptides overlapping the entire S protein sequence against the convalescent sera from SARS patients and antisera from small animals immunized with inactivated SARS-CoV. Site IV located in the middle region of the S protein (residues 528-635) is a major immunodominant epitope. The synthetic peptide S(603-634), which overlaps the site IV sequence reacted with all the convalescent sera from 42 SARS patient, but none of the 30 serum samples from healthy blood donors, suggesting its potential application as an Ag for developing SARS diagnostics. This study also provides information useful for designing SARS vaccines and understanding the SARS pathogenesis.

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Antibodies, Viral / blood
  • Computational Biology / methods
  • Epitope Mapping / methods*
  • Humans
  • Immunodominant Epitopes / administration & dosage
  • Immunodominant Epitopes / analysis*
  • Immunodominant Epitopes / immunology
  • Membrane Glycoproteins / administration & dosage
  • Membrane Glycoproteins / chemical synthesis
  • Membrane Glycoproteins / immunology*
  • Mice
  • Mice, Inbred BALB C
  • Molecular Sequence Data
  • Peptide Fragments / administration & dosage
  • Peptide Fragments / chemical synthesis
  • Peptide Fragments / immunology
  • Protein Structure, Tertiary / genetics
  • Rabbits
  • Reagent Kits, Diagnostic
  • Recombinant Proteins / administration & dosage
  • Recombinant Proteins / chemical synthesis
  • Recombinant Proteins / immunology
  • Severe Acute Respiratory Syndrome / diagnosis*
  • Severe Acute Respiratory Syndrome / immunology
  • Severe Acute Respiratory Syndrome / prevention & control*
  • Severe acute respiratory syndrome-related coronavirus / genetics
  • Severe acute respiratory syndrome-related coronavirus / immunology*
  • Spike Glycoprotein, Coronavirus
  • Vaccines, Inactivated / administration & dosage
  • Vaccines, Inactivated / chemical synthesis
  • Vaccines, Inactivated / immunology
  • Viral Envelope Proteins / administration & dosage
  • Viral Envelope Proteins / chemical synthesis
  • Viral Envelope Proteins / immunology*
  • Viral Vaccines / administration & dosage
  • Viral Vaccines / chemical synthesis
  • Viral Vaccines / immunology*

Substances

  • Antibodies, Viral
  • Immunodominant Epitopes
  • Membrane Glycoproteins
  • Peptide Fragments
  • Reagent Kits, Diagnostic
  • Recombinant Proteins
  • Spike Glycoprotein, Coronavirus
  • Vaccines, Inactivated
  • Viral Envelope Proteins
  • Viral Vaccines
  • spike glycoprotein, SARS-CoV
  • spike protein, mouse hepatitis virus