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

Choy, Wai-Yan; Lin, Shu-Guang; Chan, Paul Kay-Sheung; Tam, John Siu-Lun; Lo, Y M Dennis; Chu, Ida Miu-Ting; Tsai, Sau-Na; Zhong, Ming-Qi; Fung, Kwok-Pui; Waye, Mary Miu-Yee; Tsui, Stephen Kwok-Wing; Ng, Kai-On; Shan, Zhi-Xin; Yang, Min; Wu, Yi-Long; Lin, Zhan-Yi; Ngai, Sai-Ming

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.