title: 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.affiliation: Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College , 2A Nanwei Road, Xuanwu District, Beijing 100050, People's Republic of China.
authors.forename: Qidi
authors.initials: Q
authors.lastname: Wang
authors.affiliation: Institute of Laboratory Animal Science, Chinese Academy of Medical Sciences and Peking Union Medical College , Beijing 100021, People's Republic of China.
authors.forename: Lianfeng
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Faculty of Life Sciences, Kumamoto University , 1-1-1 Honjo, Kumamoto 860-8556, Japan.
authors.forename: Kazuhiko
authors.initials: K
authors.lastname: Kuwahara
authors.affiliation: Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College , 2A Nanwei Road, Xuanwu District, Beijing 100050, People's Republic of China.
authors.forename: Li
authors.initials: L
authors.lastname: Li
authors.affiliation: Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College , 2A Nanwei Road, Xuanwu District, Beijing 100050, People's Republic of China.
authors.forename: Zijie
authors.initials: Z
authors.lastname: Liu
authors.affiliation: Department of Infectious Disease, Peking Union Medical College Hospital and AIDS Research Center, Chinese Academy of Medical Sciences and Peking Union Medical College , Beijing 100071, People's Republic of China.
authors.forename: Taisheng
authors.initials: T
authors.lastname: Li
authors.affiliation: Institute of Laboratory Animal Science, Chinese Academy of Medical Sciences and Peking Union Medical College , Beijing 100021, People's Republic of China.
authors.forename: Hua
authors.initials: H
authors.lastname: Zhu
authors.affiliation: Institute of Laboratory Animal Science, Chinese Academy of Medical Sciences and Peking Union Medical College , Beijing 100021, People's Republic of China.
authors.forename: Jiangning
authors.initials: J
authors.lastname: Liu
authors.affiliation: Institute of Laboratory Animal Science, Chinese Academy of Medical Sciences and Peking Union Medical College , Beijing 100021, People's Republic of China.
authors.forename: Yanfeng
authors.initials: Y
authors.lastname: Xu
authors.affiliation: Department of Infectious Disease, Peking Union Medical College Hospital and AIDS Research Center, Chinese Academy of Medical Sciences and Peking Union Medical College , Beijing 100071, People's Republic of China.
authors.forename: Jing
authors.initials: J
authors.lastname: Xie
authors.affiliation: Faculty of Life Sciences, Kumamoto University , 1-1-1 Honjo, Kumamoto 860-8556, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Morioka
authors.affiliation: Faculty of Life Sciences, Kumamoto University , 1-1-1 Honjo, Kumamoto 860-8556, Japan.|WPI Immunology Frontier Research Center, Osaka University , 3-1 Yamada-oka, Suita, Osaka 565-0871, Japan.
authors.forename: Nobuo
authors.initials: N
authors.lastname: Sakaguchi
authors.affiliation: Institute of Laboratory Animal Science, Chinese Academy of Medical Sciences and Peking Union Medical College , Beijing 100021, People's Republic of China.
authors.forename: Chuan
authors.initials: C
authors.lastname: Qin
authors.affiliation: Tsinghua-Peking Center for Life Sciences & School of Pharmaceutical Sciences, Tsinghua University , Haidian District, Beijing 100084, People's Republic of China.|Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College , 2A Nanwei Road, Xuanwu District, Beijing 100050, People's Republic of China.
authors.forename: Gang
authors.initials: G
authors.lastname: Liu
mesh_terms: D000818:Animals; D057134:Antibodies, Neutralizing / Q000276:immunology; D000914:Antibodies, Viral / Q000276:immunology*; D019067:Antibody-Dependent Enhancement; D004195:Disease Models, Animal; D018985:Epitopes, B-Lymphocyte / Q000737:chemistry / Q000276:immunology*; D006801:Humans; D016056:Immunodominant Epitopes / Q000737:chemistry / Q000235:genetics / Q000276:immunology*; D008253:Macaca mulatta; D045473:Severe acute respiratory syndrome-related coronavirus / Q000737:chemistry / Q000235:genetics / Q000276:immunology*; D045169:Severe Acute Respiratory Syndrome / Q000276:immunology* / Q000821:virology; D064370:Spike Glycoprotein, Coronavirus / Q000737:chemistry / Q000235:genetics / Q000276:immunology
chemical_list: D057134:Antibodies, Neutralizing; D000914:Antibodies, Viral; D018985:Epitopes, B-Lymphocyte; D016056:Immunodominant Epitopes; D064370:Spike Glycoprotein, Coronavirus
keywords: B-cell peptide epitope; SARS-CoV; antibody-dependent enhancement (ADE); epitope sequence-dependent (ESD) enhancement; peptide; vaccine