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

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.

• Authors: Qidi Wang, Lianfeng Zhang, Kazuhiko Kuwahara, Li Li, Zijie Liu, Taisheng Li, Hua Zhu, Jiangning Liu, Yanfeng Xu, Jing Xie, Hiroshi Morioka, Nobuo Sakaguchi, Chuan Qin, Gang Liu
• Journal: ACS infectious diseases (ACS Infect Dis) Vol. 2 Issue 5 Pg. 361-76 (05 13 2016) ISSN: 2373-8227 [Electronic] United States
• PMID: 27627203 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, N.I.H., Extramural)

Chemical References

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

Topics

• Animals
• Antibodies, Neutralizing (immunology)
• Antibodies, Viral (immunology)
• Antibody-Dependent Enhancement
• Disease Models, Animal
• Epitopes, B-Lymphocyte (chemistry, immunology)
• Humans
• Immunodominant Epitopes (chemistry, genetics, immunology)
• Macaca mulatta
• Severe acute respiratory syndrome-related coronavirus (chemistry, genetics, immunology)
• Severe Acute Respiratory Syndrome (immunology, virology)
• Spike Glycoprotein, Coronavirus (chemistry, genetics, immunology)