title: Recombinant rabies virus expressing dog GM-CSF is an efficacious oral rabies vaccine for dogs.
abstract: Developing efficacious oral rabies vaccines is an important step to increase immunization coverage for stray dogs, which are not accessible for parenteral vaccination. Our previous studies have demonstrated that recombinant rabies virus (RABV) expressing cytokines/chemokines induces robust protective immune responses after oral immunization in mice by recruiting and activating dendritic cells (DCs) and B cells. To develop an effective oral rabies vaccine for dogs, a recombinant attenuated RABV expressing dog GM-CSF, designated as LBNSE-dGM-CSF was constructed and used for oral vaccination in a dog model. Significantly more DCs or B cells were activated in the peripheral blood of dogs vaccinated orally with LBNSE-dGM-CSF than those vaccinated with the parent virus LBNSE, particularly at 3 days post immunization (dpi). As a result, significantly higher levels of virus neutralizing antibodies (VNAs) were detected in dogs immunized with LBNSE-dGM-CSF than with the parent virus. All the immunized dogs were protected against a lethal challenge with 4500 MICLD50 of wild-type RABV SXTYD01. LBNSE-dGM-CSF was found to replicate mainly in the tonsils after oral vaccination as detected by nested RT-PCR and immunohistochemistry. Taken together, our results indicate that LBNSE-dGM-CSF could be a promising oral rabies vaccine candidate for dogs.
authors.affiliation: State Key Laboratory of Agricultural Microbiology, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, China.
authors.forename: Ming
authors.initials: M
authors.lastname: Zhou
authors.affiliation: State Key Laboratory of Agricultural Microbiology, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Wang
authors.affiliation: State Key Laboratory of Agricultural Microbiology, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, China.
authors.forename: Songqin
authors.initials: S
authors.lastname: Zhou
authors.affiliation: State Key Laboratory of Agricultural Microbiology, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, China.
authors.forename: Zhao
authors.initials: Z
authors.lastname: Wang
authors.affiliation: State Key Laboratory of Agricultural Microbiology, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, China.
authors.forename: Juncheng
authors.initials: J
authors.lastname: Ruan
authors.affiliation: Hubei Provincial Key Laboratory for Applied Toxicology, Hubei Provincial Academy of Preventive Medicine, Wuhan, China.
authors.forename: Lijun
authors.initials: L
authors.lastname: Tang
authors.affiliation: Hubei Provincial Key Laboratory for Applied Toxicology, Hubei Provincial Academy of Preventive Medicine, Wuhan, China.
authors.forename: Ziming
authors.initials: Z
authors.lastname: Jia
authors.affiliation: State Key Laboratory of Agricultural Microbiology, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, China.
authors.forename: Min
authors.initials: M
authors.lastname: Cui
authors.affiliation: State Key Laboratory of Agricultural Microbiology, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, China.
authors.forename: Ling
authors.initials: L
authors.lastname: Zhao
authors.affiliation: State Key Laboratory of Agricultural Microbiology, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, China.|Department of Pathology, University of Georgia, Athens, GA, USA.
authors.forename: Zhen F
authors.initials: ZF
authors.lastname: Fu
mesh_terms: D000284:Administration, Oral; D000818:Animals; D004283:Dog Diseases / Q000517:prevention & control* / Q000821:virology; D004285:Dogs; D005260:Female; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology*; D011818:Rabies / Q000517:prevention & control / Q000662:veterinary*; D011819:Rabies Vaccines / Q000235:genetics / Q000276:immunology*; D011820:Rabies virus / Q000276:immunology*; D011897:Random Allocation; D014614:Vaccines, Synthetic / Q000235:genetics / Q000276:immunology
chemical_list: D011819:Rabies Vaccines; D014614:Vaccines, Synthetic; D016178:Granulocyte-Macrophage Colony-Stimulating Factor
keywords: GM-CSF; Immune response; Immunity; Immunology and Microbiology Section; dog; oral vaccine; rabies; recombinant rabies virus