title: Glycoprotein from street rabies virus BD06 induces early and robust immune responses when expressed from a non-replicative adenovirus recombinant.
abstract: The rabies virus (RABV) glycoprotein (G) is responsible for inducing neutralizing antibodies against rabies virus. Development of recombinant vaccines using the G genes from attenuated strains rather than street viruses is a regular practice. In contrast to this scenario, we generated three human adenovirus type 5 recombinants using the G genes from the vaccine strains SRV9 and Flury-LEP, and the street RABV strain BD06 (nrAd5-SRV9-G, nrAd5-Flury-LEP-G, and nrAd5-BD06-G). These recombinants were non-replicative, but could grow up to ~10(8) TCID50/ml in helper HEK293AD cells. Expression of the G protein was verified by immunostaining, quantitative PCR and cytometry. Animal experiments revealed that immunization with nrAd5-BD06-G can induce a higher seroconversion rate, a higher neutralizing antibody level, and a longer survival time after rabies virus challenge in mice when compared with the other two recombinants. Moreover, the expression of granulocyte-macrophage colony-stimulating factor (GM-CSF) was significantly higher in mice immunized with nrAd5-BD06-G, which might also contribute to the increased protection. These results show that the use of street RABV G for non-replicative systems may be an alternative for developing effective recombinant rabies vaccines.
authors.affiliation: Laboratory of Epidemiology and Key Laboratory of Jilin Province for Zoonosis Prevention and Control, Veterinary Research Institute, Academy of Military Medical Sciences, 666 Liuying West Road, Jingyue Economic Development Zone, Changchun, 130122, China.
authors.forename: Shuchao
authors.initials: S
authors.lastname: Wang
authors.forename: Chenglong
authors.initials: C
authors.lastname: Sun
authors.forename: Shoufeng
authors.initials: S
authors.lastname: Zhang
authors.forename: Xiaozhuo
authors.initials: X
authors.lastname: Zhang
authors.forename: Ye
authors.initials: Y
authors.lastname: Liu
authors.forename: Ying
authors.initials: Y
authors.lastname: Wang
authors.forename: Fei
authors.initials: F
authors.lastname: Zhang
authors.forename: Xianfu
authors.initials: X
authors.lastname: Wu
authors.forename: Rongliang
authors.initials: R
authors.lastname: Hu
mesh_terms: D000260:Adenoviruses, Human / Q000235:genetics*; D000818:Animals; D057134:Antibodies, Neutralizing / Q000097:blood; D000914:Antibodies, Viral / Q000097:blood; D000956:Antigens, Viral / Q000235:genetics / Q000276:immunology*; D004337:Drug Carriers; D005260:Female; D005822:Genetic Vectors; D006023:Glycoproteins / Q000235:genetics / Q000276:immunology*; D051379:Mice; D011819:Rabies Vaccines / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*; D011820:Rabies virus / Q000235:genetics / Q000276:immunology*; D016019:Survival Analysis; D014613:Vaccines, Attenuated / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology; D014614:Vaccines, Synthetic / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology; D014759:Viral Envelope Proteins / Q000235:genetics / Q000276:immunology*
chemical_list: D057134:Antibodies, Neutralizing; D000914:Antibodies, Viral; D000956:Antigens, Viral; D004337:Drug Carriers; D006023:Glycoproteins; D011819:Rabies Vaccines; D014613:Vaccines, Attenuated; D014614:Vaccines, Synthetic; D014759:Viral Envelope Proteins; C064951:glycoprotein G, Rabies virus