TY - JOUR
T1 - Immunodominant SARS coronavirus epitopes in humans elicited both enhancing and neutralizing effects on infection in non-human primates
AU - Wang, Qidi
AU - Zhang, Lianfeng
AU - Kuwahara, Kazuhiko
AU - Li, Li
AU - Liu, Zijie
AU - Li, Taisheng
AU - Zhu, Hua
AU - Liu, Jiangning
AU - Xu, Yanfeng
AU - Xie, Jing
AU - Morioka, Hiroshi
AU - Sakaguchi, Nobuo
AU - Qin, Chuan
AU - Liu, Gang
N1 - Funding Information:
We are grateful to Professor Carl F. Nathan and Dr. Michael S. Diamond for their kind discussion and manuscript preparation. We thank Dr. Baoxing Fan for his serological evaluation of the large number of SARS-CoV convalescent antisera. The project described in this paper was supported by the National Institute of Allergy and Infectious Diseases (U01AI061092). The study was also partially supported for preparation of the monoclonal antibodies by contract research for MEXT for Emerging and Reemerging Infectious Diseases and Promotion of Fundamental Studies in Health Sciences (04-2) of the NIBIO and National Natural Science Foundation of China (No. 90713045).
PY - 2016/5/13
Y1 - 2016/5/13
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=84991518731&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84991518731&partnerID=8YFLogxK
U2 - 10.1021/acsinfecdis.6b00006
DO - 10.1021/acsinfecdis.6b00006
M3 - Article
C2 - 27627203
AN - SCOPUS:84991518731
VL - 2
SP - 361
EP - 376
JO - ACS Infectious Diseases
JF - ACS Infectious Diseases
SN - 2373-8227
IS - 5
ER -