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Clinical Chemistry 50: 1036-1042, 2004. First published March 25, 2004; 10.1373/clinchem.2003.029801
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(Clinical Chemistry. 2004;50:1036-1042.)
© 2004 American Association for Clinical Chemistry, Inc.

Clinical Immunology

Synthetic Peptide Studies on the Severe Acute Respiratory Syndrome (SARS) Coronavirus Spike Glycoprotein: Perspective for SARS Vaccine Development

Wai-Yan Choy1, Shu-Guang Lin6, Paul Kay-Sheung Chan2, John Siu-Lun Tam2, Y.M. Dennis Lo3, Ida Miu-Ting Chu2, Sau-Na Tsai4, Ming-Qi Zhong1, Kwok-Pui Fung5, Mary Miu-Yee Waye5, Stephen Kwok-Wing Tsui5, Kai-On Ng3, Zhi-Xin Shan6, Min Yang6, Yi-Long Wu6, Zhan-Yi Lin6 and Sai-Ming Ngai1,4,a

1 Molecular Biotechnology Program, Department of Biology and Department of Biochemistry, and Departments of 2 Microbiology, 3 Chemical Pathology, 4 Biology, and 5 Biochemistry, The Chinese University of Hong Kong, Shatin, Hong Kong. 6 Research Center of Medical Sciences, Guangdong Provincial People’s Hospital, Guangdong, China.

aAddress correspondence to this author at: Department of Biology, The Chinese University of Hong Kong, Shatin, Hong Kong. Fax 852-26035646; e-mail smngai{at}cuhk.edu.hk.

Background: The S (spike) protein of the etiologic coronavirus (CoV) agent of severe acute respiratory syndrome (SARS) plays a central role in mediating viral infection via receptor binding and membrane fusion between the virion and the host cell. We focused on using synthetic peptides for developing antibodies against SARS-CoV, which aimed to block viral invasion by eliciting an immune response specific to the native SARS-CoV S protein.

Methods: Six peptide sequences corresponding to the surface regions of SARS-CoV S protein were designed and investigated by use of combined bioinformatics and structural analysis. These synthetic peptides were used to immunize both rabbits and monkeys. Antisera collected 1 week after the second immunization were analyzed by ELISA and tested for antibody specificity against SARS-CoV by immunofluorescent confocal microscopy.

Results: Four of our six synthetic peptides (S2, S3, S5, and S6) elicited SARS-CoV-specific antibodies, of which S5 (residues 788–820) and S6 (residues 1002–1030) exhibited immunogenic responses similar to those found in a parallel investigation using truncated recombinant protein analogs of the SARS-CoV S protein. This suggested that our S5 and S6 peptides may represent two minimum biologically active sequences of the immunogenic regions of the SARS-CoV S protein.

Conclusions: Synthetic peptides can elicit specific antibodies to SARS-CoV. The study provides insights for the future development of SARS vaccine via the synthetic-peptide-based approach.




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