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 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.
Du
Lanying
L
Department of Microbiology, The University of Hong Kong, Pokfulam, Hong Kong SAR, China.
He
Yuxian
Y
Wang
Yijia
Y
Zhang
Haojie
H
Ma
Selene
S
Wong
Charlotte K L
CK
Wu
Sharon H W
SH
Ng
Fai
F
Huang
Jian-Dong
JD
Yuen
Kwok-Yung
KY
Jiang
Shibo
S
Zhou
Yusen
Y
Zheng
Bo-Jian
BJ
D000818:Animals; D000914:Antibodies, Viral / Q000096:biosynthesis; D002460:Cell Line; D000229:Dependovirus / Q000235:genetics* / Q000378:metabolism*; D005260:Female; D005822:Genetic Vectors; D006367:HeLa Cells; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D009500:Neutralization Tests; D017434:Protein Structure, Tertiary; D011991:Receptors, Virus / Q000378:metabolism*; D011994:Recombinant Proteins / Q000378:metabolism; D045473:Severe acute respiratory syndrome-related coronavirus / Q000276:immunology*; D014765:Viral Vaccines / Q000276:immunology*
D000914:Antibodies, Viral; D011991:Receptors, Virus; D011994:Recombinant Proteins; D014765:Viral Vaccines