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Journal of Virology, March 2005, p. 3401-3408, Vol. 79, No. 6
0022-538X/05/$08.00+0     doi:10.1128/JVI.79.6.3401-3408.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

B-Cell Responses in Patients Who Have Recovered from Severe Acute Respiratory Syndrome Target a Dominant Site in the S2 Domain of the Surface Spike Glycoprotein

Xiaofen Zhong,1 Huanghao Yang,1,2 Zu-Feng Guo,1,2 Wan-Yee Fion Sin,3 Wei Chen,4 Junjie Xu,4 Ling Fu,4 Jie Wu,1 Chun-Kit Gannon Mak,1 Chak-Sum Samuel Cheng,3 Yanzhen Yang,1 Shuyong Cao,1 Tin-Yau Wong,5 Sik-To Lai,5 Yong Xie,3* and Zhihong Guo1,2*

Department of Chemistry,1 Biotechnology Research Institute,2 Department of Biology, The Hong Kong University of Science and Technology, Clear Water Bay, Kowloon,3 Princess Margaret Hospital, Hong Kong SAR,5 Institute of Microbiology and Epidemiology, Academy of Military Medical Sciences, Beijing, China4

Received 23 July 2004/ Accepted 22 October 2004

Severe acute respiratory syndrome (SARS) is a recently emerged infectious disease caused by a novel strain of coronavirus. Examination of the immune responses of patients who have recovered from SARS should provide important information for design of a safe and effective vaccine. We determined the continuous viral epitopes targeted by antibodies in plasma samples from convalescent SARS patients through biopanning with a vast M13 phage display dodecapeptide library. These epitopes converged to very short peptide fragments, one on each of the structural proteins spike and nucleocapsid and the nonstructural proteins 3a, 9b, and nsp 3. Immunoassays found that most of the patients who had recovered from SARS developed complementary antibodies to the epitope-rich region on the spike S2 protein, indicating that this is an immunodominant site on the viral envelope comprising the spike, matrix, and small envelope glycoproteins. These S2-targeting antibodies were shown to effectively neutralize the coronavirus, indicating that they provided protective immunity to help the patients recover from the viral infection. These results suggest that the SARS coronavirus might have an antigenic profile distinct from those of other human or animal coronaviruses. Due to the tested safety and protective effects of the convalescent-phase serological antibodies, identification of their complementary antigens may enable the design of an epitope-based vaccine to prevent potential antibody-mediated immunuopathology.

* Corresponding author. Mailing address for Zhihong Guo: Department of Chemistry, The Hong Kong University of Science and Technology, Clear Water Bay, Kowloon, Hong Kong SAR, China. Phone: 852-2358-7352. Fax: 852-2358-1594. E-mail: chguo{at}ust.hk. Mailing address for Yong Xie: Department of Biology, The Hong Kong University of Science and Technology, Clear Water Bay, Kowloon, Hong Kong SAR, China. Phone: 852-2358-7340. Fax: 852-2358-1559. E-mail: boyxie@ust.hk.

Journal of Virology, March 2005, p. 3401-3408, Vol. 79, No. 6
0022-538X/05/$08.00+0     doi:10.1128/JVI.79.6.3401-3408.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.



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