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

• Published in: ACS infectious diseases Vol. 2; no. 5; pp. 361 - 376
• Main Authors: Wang, Qidi, Zhang, Lianfeng, Kuwahara, Kazuhiko, Li, Li, Liu, Zijie, Li, Taisheng, Zhu, Hua, Liu, Jiangning, Xu, Yanfeng, Xie, Jing, Morioka, Hiroshi, Sakaguchi, Nobuo, Qin, Chuan, Liu, Gang
• Format: Journal Article
• Language: English
• Published: United States American Chemical Society 13.05.2016
• Subjects: 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; peptide; vaccine; antibody-dependent enhancement (ADE); epitope sequence-dependent (ESD) enhancement; B-cell peptide epitope; SARS-CoV
• ISSN: 2373-8227; 2373-8227
• DOI: 10.1021/acsinfecdis.6b00006

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.