Monoclonal Antibodies targeting the HR2 Domain and the region immediately upstream of the HR2 of the S Protein neutralize in Vitro Infection of Severe Acute Respiratory Syndrome Coronavirus
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Date
2006Author
Lip, Kuo-Ming
Shen, Shuo
Yang, Xiaoming
Keng, Choong-Tat
Zhang, Aihua
Oh, Hsueh-Ling Janice
Li, Zhi-Hong
Hwang, Le-Ann
Chou, Chih-Fong
Fielding, Burtram C.
Tan, Timothy H.P.
Mayrhofer, Josef
Falkner, Falko G.
Fu, Jianlin
Lim, Seng Gee
Hong, Wanjin
Tan, Yee-Joo
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Show full item recordAbstract
We have previously shown that an Escherichia coli-expressed, denatured spike (S) protein fragment of the
severe acute respiratory coronavirus, containing residues 1029 to 1192 which include the heptad repeat 2
(HR2) domain, was able to induce neutralizing polyclonal antibodies (C. T. Keng, A. Zhang, S. Shen, K. M. Lip,
B. C. Fielding, T. H. Tan, C. F. Chou, C. B. Loh, S. Wang, J. Fu, X. Yang, S. G. Lim, W. Hong, and Y. J. Tan,
J. Virol. 79:3289–3296, 2005). In this study, monoclonal antibodies (MAbs) were raised against this fragment
to identify the linear neutralizing epitopes in the functional domain and to investigate the mechanisms involved
in neutralization. Eighteen hybridomas secreting the S protein-specific MAbs were obtained. Binding sites of
these MAbs were mapped to four linear epitopes. Two of them were located within the HR2 region and two
immediately upstream of the HR2 domain. MAbs targeting these epitopes showed in vitro neutralizing
activities and were able to inhibit cell-cell membrane fusion. These results provide evidence of novel neutralizing
epitopes that are located in the HR2 domain and the spacer region immediately upstream of the HR2 of
the S protein.