Immunodominant SARS Coronavirus Epitopes in Humans Elicited both Enhancing and Neutralizing Effects on Infection in Non-human Primates

ACS Infect Dis. 2016 May 13;2(5):361-76. doi: 10.1021/acsinfecdis.6b00006. Epub 2016 Apr 11.

Abstract

Severe acute respiratory syndrome (SARS) is caused by a coronavirus (SARS-CoV) and has the potential to threaten global public health and socioeconomic stability. Evidence of antibody-dependent enhancement (ADE) of SARS-CoV infection in vitro and in non-human primates clouds the prospects for a safe vaccine. Using antibodies from SARS patients, we identified and characterized SARS-CoV B-cell peptide epitopes with disparate functions. In rhesus macaques, the spike glycoprotein peptides S471-503, S604-625, and S1164-1191 elicited antibodies that efficiently prevented infection in non-human primates. In contrast, peptide S597-603 induced antibodies that enhanced infection both in vitro and in non-human primates by using an epitope sequence-dependent (ESD) mechanism. This peptide exhibited a high level of serological reactivity (64%), which resulted from the additive responses of two tandem epitopes (S597-603 and S604-625) and a long-term human B-cell memory response with antisera from convalescent SARS patients. Thus, peptide-based vaccines against SARS-CoV could be engineered to avoid ADE via elimination of the S597-603 epitope. We provide herein an alternative strategy to prepare a safe and effective vaccine for ADE of viral infection by identifying and eliminating epitope sequence-dependent enhancement of viral infection.

Keywords: B-cell peptide epitope; SARS-CoV; antibody-dependent enhancement (ADE); epitope sequence-dependent (ESD) enhancement; peptide; vaccine.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Antibodies, Neutralizing / immunology
  • Antibodies, Viral / immunology*
  • Antibody-Dependent Enhancement*
  • Disease Models, Animal
  • Epitopes, B-Lymphocyte / chemistry
  • Epitopes, B-Lymphocyte / immunology*
  • Humans
  • Immunodominant Epitopes / chemistry
  • Immunodominant Epitopes / genetics
  • Immunodominant Epitopes / immunology*
  • Macaca mulatta
  • SARS Virus / chemistry
  • SARS Virus / genetics
  • SARS Virus / immunology*
  • Severe Acute Respiratory Syndrome / immunology*
  • Severe Acute Respiratory Syndrome / virology
  • Spike Glycoprotein, Coronavirus / chemistry
  • Spike Glycoprotein, Coronavirus / genetics
  • Spike Glycoprotein, Coronavirus / immunology

Substances

  • Antibodies, Neutralizing
  • Antibodies, Viral
  • Epitopes, B-Lymphocyte
  • Immunodominant Epitopes
  • Spike Glycoprotein, Coronavirus