Immunodominant SARS coronavirus epitopes in humans elicited both enhancing and neutralizing effects on infection in non-human primates

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

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60 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)361-376
Number of pages16
JournalACS Infectious Diseases
Volume2
Issue number5
DOIs
Publication statusPublished - 13-05-2016

All Science Journal Classification (ASJC) codes

  • Infectious Diseases

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    Wang, Q., Zhang, L., Kuwahara, K., Li, L., Liu, Z., Li, T., Zhu, H., Liu, J., Xu, Y., Xie, J., Morioka, H., Sakaguchi, N., Qin, C., & Liu, G. (2016). Immunodominant SARS coronavirus epitopes in humans elicited both enhancing and neutralizing effects on infection in non-human primates. ACS Infectious Diseases, 2(5), 361-376. https://doi.org/10.1021/acsinfecdis.6b00006