Recombinant adeno-associated virus expressing the receptor-binding domain of severe acute respiratory syndrome coronavirus S protein elicits neutralizing antibodies: Implication for developing SARS vaccines

• Published in: Virology (New York, N.Y.) N.Y.), 2006-09, Vol.353 (1), p.6-16
• Main Authors: Du, Lanying, He, Yuxian, Wang, Yijia, Zhang, Haojie, Ma, Selene, Wong, Charlotte K.L., Wu, Sharon H.W., Ng, Fai, Huang, Jian-Dong, Yuen, Kwok-Yung, Jiang, Shibo, Zhou, Yusen, Zheng, Bo-Jian
• Format: Article
• Language: English
• Subjects: Adeno-associated virus; Animals; Antibodies, Viral - biosynthesis; Cell Line; Dependovirus - genetics; Dependovirus - metabolism; Female; Genetic Vectors; HeLa Cells; Humans; Mice; Mice, Inbred BALB C; Neutralization Tests; Neutralizing antibodies; Protein Structure, Tertiary; Receptor-binding domain; Receptors, Virus - metabolism; Recombinant Proteins - metabolism; SARS coronavirus; SARS Virus - immunology; SARS-CoV; Spike protein; Vaccines; Viral Vaccines - immunology
• ISSN: 0042-6822; 1096-0341
• DOI: 10.1016/j.virol.2006.03.049

Development of an effective vaccine for severe acute respiratory syndrome (SARS) remains to be a priority to prevent possible re-emergence of SARS coronavirus (SARS-CoV). We previously demonstrated that the receptor-binding domain (RBD) of SARS-CoV S protein is a major target of neutralizing antibodies. This suggests that the RBD may serve as an ideal vaccine candidate. Recombinant adeno-associated virus (rAAV) has been proven to be an effective system for gene delivery and vaccine development. In this study, a novel vaccine against SARS-CoV was developed based on the rAAV delivery system. The gene encoding RBD was cloned into a pAAV-IRES-hrGFP plasmid. The immunogenicity induced by the resulting recombinant RBD-rAAV was evaluated in BALB/c mice. The results demonstrated that (1) a single dose of RBD-rAAV vaccination could induce sufficient neutralizing antibody against SARS-CoV infection; (2) two more repeated doses of the vaccination boosted the neutralizing antibody to about 5 times of the level achieved by a single dose of the immunization and (3) the level of the antibody continued to increase for the entire duration of the experiment of 5.5 months. These results suggested that RBD-rAAV is a promising SARS candidate vaccine.