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

详细信息    查看全文

• 作者：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
• 刊名：ACS Infectious Diseases
• 出版年：2016
• 出版时间：May 13, 2016
• 年：2016
• 卷：2
• 期：5
• 页码：361-376
• 全文大小：1172K
• ISSN：2373-8227

文摘

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 S_471–503, S_604–625, and S_1164–1191 elicited antibodies that efficiently prevented infection in non-human primates. In contrast, peptide S_597–603 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 (S_597–603 and S_604–625) 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 S_597–603 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.