title: Genetically modified rabies virus ERA strain is safe and induces long-lasting protective immune response in dogs after oral vaccination.
abstract: Oral immunization in free-roaming dogs is one of the most practical approaches to prevent rabies for developing countries. The safe, efficient and long-lasting protective oral rabies vaccine for dogs is highly sought. In this study, rabies virus (RABV) Evelyn-Rokitnicki-Abelseth (ERA) strain wild-type (rERA) and a genetically modified type (rERAG333E) containing a mutation from arginine to glutamic acid at residue 333 of glycoprotein (G333E) were generated by reverse genetic. The recombinant virus rERAG333E retained growth properties of similar to the parent strain rERA in BHK-21 cell culture. The G333E mutation showed genetic stability during passage into neuroblastoma cells and in the brains of suckling mice and was significantly reduced the virulence of rERA in mice. rERAG333E was immunogenic in dogs by intramuscular inoculation. Mice orally vaccinated with rERAG333E induced strong and one year longer virus neutralizing antibodies (VNA) to RABV, and were completely protected from challenge with lethal street virus at 12months after immunization. Dogs received oral vaccination with rERAG333E induced strong protective RABV VNA response, which lasted for over 3years, and moderate saliva RABV-specific IgA. Moreover, sizeable booster responses to RABV VNA were induced by a second oral dose 1year after the first dose. These results demonstrated that the genetically modified ERA vaccine strain has the potential to serve as a safe and efficient oral live vaccine against rabies in dogs.
authors.affiliation: Key Laboratory of Veterinary Public Health of Ministry of Agriculture, State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Harbin 150001, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Shuai
authors.affiliation: Key Laboratory of Jilin Province for Zoonosis Prevention and Control, Institute of Military Veterinary, Academy of Military Medical Sciences, Changchun 130122, China.
authors.forename: Na
authors.initials: N
authors.lastname: Feng
authors.affiliation: Key Laboratory of Veterinary Public Health of Ministry of Agriculture, State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Harbin 150001, China.
authors.forename: Xijun
authors.initials: X
authors.lastname: Wang
authors.affiliation: Key Laboratory of Veterinary Public Health of Ministry of Agriculture, State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Harbin 150001, China.
authors.forename: Jinying
authors.initials: J
authors.lastname: Ge
authors.affiliation: Key Laboratory of Veterinary Public Health of Ministry of Agriculture, State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Harbin 150001, China.
authors.forename: Zhiyuan
authors.initials: Z
authors.lastname: Wen
authors.affiliation: Key Laboratory of Veterinary Public Health of Ministry of Agriculture, State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Harbin 150001, China.
authors.forename: Weiye
authors.initials: W
authors.lastname: Chen
authors.affiliation: Key Laboratory of Veterinary Public Health of Ministry of Agriculture, State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Harbin 150001, China.
authors.forename: Lide
authors.initials: L
authors.lastname: Qin
authors.affiliation: Key Laboratory of Jilin Province for Zoonosis Prevention and Control, Institute of Military Veterinary, Academy of Military Medical Sciences, Changchun 130122, China.
authors.forename: Xianzhu
authors.initials: X
authors.lastname: Xia
authors.affiliation: Key Laboratory of Veterinary Public Health of Ministry of Agriculture, State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Harbin 150001, China. Electronic address: buzhigao@caas.cn.
authors.forename: Zhigao
authors.initials: Z
authors.lastname: Bu
mesh_terms: D000284:Administration, Oral; D019943:Amino Acid Substitution; D000818:Animals; D057134:Antibodies, Neutralizing / Q000097:blood; D000914:Antibodies, Viral / Q000097:blood; D004283:Dog Diseases / Q000517:prevention & control*; D004285:Dogs; D005260:Female; D042822:Genomic Instability; D006023:Glycoproteins / Q000235:genetics; D007156:Immunologic Memory; D007273:Injections, Intramuscular; D008807:Mice, Inbred BALB C; D050505:Mutant Proteins / Q000235:genetics; D010446:Peptide Fragments / Q000235:genetics; D011818:Rabies / Q000517:prevention & control / Q000662:veterinary*; D011819:Rabies Vaccines / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*; D011820:Rabies virus / Q000235:genetics / Q000276:immunology* / Q000502:physiology; D059386:Reverse Genetics; D016019:Survival Analysis; D013997:Time Factors; D014613:Vaccines, Attenuated / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology; D014614:Vaccines, Synthetic / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology; D014764:Viral Proteins / Q000235:genetics; D014774:Virulence; D014779:Virus Replication
chemical_list: D057134:Antibodies, Neutralizing; D000914:Antibodies, Viral; D006023:Glycoproteins; D050505:Mutant Proteins; D010446:Peptide Fragments; D011819:Rabies Vaccines; D014613:Vaccines, Attenuated; D014614:Vaccines, Synthetic; D014764:Viral Proteins; C583075:rabies virus glycoprotein peptide
keywords: Genetically modified rabies virus; Oral vaccine; Rabies virus