A recombinant rabies virus encoding two copies of the glycoprotein gene confers protection in dogs against a virulent challenge.
The rabies virus (RABV) glycoprotein (G) is the principal antigen responsible for the induction of virus neutralizing antibodies (VNA) and is the major modality of protective immunity in animals. A recombinant RABV HEP-Flury strain was generated by reverse genetics to encode two copies of the G-gene (referred to as HEP-dG). The biological properties of HEP-dG were compared to those of the parental virus (HEP-Flury strain). The HEP-dG recombinant virus grew 100 times more efficiently in BHK-21 cell than the parental virus, yet the virulence of the dG recombinant virus in suckling mice was lower than the parental virus. The HEP-dG virus can improve the expression of G-gene mRNA and the G protein and produce more offspring viruses in cells. The amount of G protein revealed a positive relationship with immunogenicity in mice and dogs. The inactivated HEP-dG recombinant virus induced higher levels of VNA and conferred better protection against virulent RABV in mice and dogs than the inactivated parental virus and a commercial vaccine. The protective antibody persisted for at least 12 months. These data demonstrate that the HEP-dG is stable, induces a strong VNA response and confers protective immunity more effectively than the RABV HEP-Flury strain. HEP-dG could be a potential candidate in the development of novel inactivated rabies vaccines.
College of Veterinary Medicine, South China Agricultural University, Guangzhou, China.
Xiaohui
X
Liu
College of Veterinary Medicine, South China Agricultural University, Guangzhou, China.
Youtian
Y
Yang
College of Veterinary Medicine, South China Agricultural University, Guangzhou, China.
Zhaojin
Z
Sun
College of Veterinary Medicine, South China Agricultural University, Guangzhou, China.
Jing
J
Chen
College of Veterinary Medicine, South China Agricultural University, Guangzhou, China.
Jun
J
Ai
College of Veterinary Medicine, South China Agricultural University, Guangzhou, China.
Can
C
Dun
State-key Laboratory of Agricultural Microbiology, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, China ; Department of Pathology, College of Veterinary Medicine, University of Georgia, Athens, Georgia, United States of America.
Zhen F
ZF
Fu
College of Veterinary Medicine, South China Agricultural University, Guangzhou, China ; Department of Pathology, College of Veterinary Medicine, University of Georgia, Athens, Georgia, United States of America.
Xuefeng
X
Niu
College of Veterinary Medicine, South China Agricultural University, Guangzhou, China.
Xiaofeng
X
Guo
D000818:Animals; D000833:Animals, Suckling; D000914:Antibodies, Viral / Q000276:immunology; D015153:Blotting, Western; D002460:Cell Line; D045744:Cell Line, Tumor; D004283:Dog Diseases / Q000276:immunology* / Q000821:virology; D004285:Dogs; D005260:Female; D015967:Gene Expression Regulation, Viral; D006023:Glycoproteins / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D006801:Humans; D007114:Immunization; D051379:Mice; D011818:Rabies / Q000276:immunology* / Q000662:veterinary / Q000821:virology; D011819:Rabies Vaccines / Q000276:immunology*; D011820:Rabies virus / Q000235:genetics / Q000276:immunology* / Q000472:pathogenicity; D011995:Recombination, Genetic; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013997:Time Factors; D015164:Vaccines, Inactivated / Q000276:immunology; D014764:Viral Proteins / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D014774:Virulence / Q000235:genetics / Q000276:immunology
D000914:Antibodies, Viral; D006023:Glycoproteins; D011819:Rabies Vaccines; D015164:Vaccines, Inactivated; D014764:Viral Proteins