title: An inactivated recombinant rabies CVS-11 virus expressing two copies of the glycoprotein elicits a higher level of neutralizing antibodies and provides better protection in mice.
abstract: The rabies virus (RABV) G protein is the primary contributor to the pathogenicity and protective immunity of RABV. In this study, we generated a recombinant rCVS-11-G strain containing two copies of the G protein derived from the pathogenic wild-type (wt) CVS-11 strain and based on its infectious clone. Compared with the wtCVS-11 strain, the rCVS-11-G strain possessed a larger virion and 1.4-fold more G protein, but it exhibited a similar growth property to the rCVS-11 strain, including passaging stability in vitro. qPCR results showed that the two G genes were over-expressed in BHK-21 cells infected with the rCVS-11-G strain. However, the rCVS-11-G strain presented an 80 % lower LD50 than the wtCVS-11 strain when intracranially (i.c.) inoculated in adult mice. Adult mice that were either intracranially (i.c.) or intramuscularly (i.m.) inoculated with rCVS-11-G strain developed more acute neurological symptoms and greater mortality than those inoculated with the wtCVS-11 strain. Furthermore, the rCVS-11-G strain was more easily and rapidly taken up by neuroblastoma cells. These data indicated that the rCVS-11-G strain might have increased neurotropism because of the over-expression of the pathogenic G protein. The inactivated rCVS-11-G strain induced significantly higher levels of virus neutralization antibodies and provided better protection from street rabies virus challenge in mice. Therefore, the rCVS-11-G strain may be a promising inactivated vaccine strain due to its better immunogenicity.
authors.affiliation: College of Veterinary Medicine, Jilin University, Changchun, 130062, China.
authors.forename: Xiang-Hong
authors.initials: XH
authors.lastname: Xue
authors.forename: Xue-Xing
authors.initials: XX
authors.lastname: Zheng
authors.forename: Hua-Lei
authors.initials: HL
authors.lastname: Wang
authors.forename: Jin-Zhu
authors.initials: JZ
authors.lastname: Ma
authors.forename: Ling
authors.initials: L
authors.lastname: Li
authors.forename: Wei-Wei
authors.initials: WW
authors.lastname: Gai
authors.forename: Tie-Cheng
authors.initials: TC
authors.lastname: Wang
authors.forename: Song-Tao
authors.initials: ST
authors.lastname: Yang
authors.forename: Xian-Zhu
authors.initials: XZ
authors.lastname: Xia
mesh_terms: D000818:Animals; D057134:Antibodies, Neutralizing / Q000276:immunology*; D000914:Antibodies, Viral / Q000276:immunology; D005260:Female; D006023:Glycoproteins / Q000008:administration & dosage / Q000276:immunology; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D011818:Rabies / Q000276:immunology* / Q000517:prevention & control* / Q000821:virology; D011819:Rabies Vaccines / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*; D011820:Rabies virus / Q000235:genetics / Q000276:immunology*; D015164:Vaccines, Inactivated / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology; D014759:Viral Envelope Proteins / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*
chemical_list: D057134:Antibodies, Neutralizing; D000914:Antibodies, Viral; D006023:Glycoproteins; D011819:Rabies Vaccines; D015164:Vaccines, Inactivated; D014759:Viral Envelope Proteins