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

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 antibod...

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Bibliographic Details
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
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Summary: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.
ISSN:0042-6822
1096-0341
DOI:10.1016/j.virol.2006.03.049