title: Immunogenicity of multi-epitope-based vaccine candidates administered with the adjuvant Gp96 against rabies.
abstract: Rabies, a zoonotic disease, causes > 55,000 human deaths globally and results in at least 500 million dollars in losses every year. The currently available rabies vaccines are mainly inactivated and attenuated vaccines, which have been linked with clinical diseases in animals. Thus, a rabies vaccine with high safety and efficacy is urgently needed. Peptide vaccines are known for their low cost, simple production procedures and high safety. Therefore, in this study, we examined the efficacy of multi-epitope-based vaccine candidates against rabies virus. The ability of various peptides to induce epitope-specific responses was examined, and the two peptides that possessed the highest antigenicity and conservation, i.e., AR16 and hPAB, were coated with adjuvant canine-Gp96 and used to prepare vaccines. The peptides were prepared as an emulsion of oil in water (O/W) to create three batches of bivalent vaccine products. The vaccine candidates possessed high safety. Virus neutralizing antibodies were detected on the day 14 after the first immunization in mice and beagles, reaching 5-6 IU/mL in mice and 7-9 IU/mL in beagles by day 28. The protective efficacy of the vaccine candidates was about 70%-80% in mice challenged by a virulent strain of rabies virus. Thus, a novel multi-epitope-based rabies vaccine with Gp96 as an adjuvant was developed and validated in mice and dogs. Our results suggest that synthetic peptides hold promise for the development of novel vaccines against rabies.
authors.affiliation: Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing, 100101, China.|University of Chinese Academy of Sciences, Beijing, 100049, China.
authors.forename: Yange
authors.initials: Y
authors.lastname: Niu
authors.affiliation: Laboratory of Epidemiology and Key Laboratory of Jilin Province for Zoonosis Prevention and Control, Veterinary Research Institute, Academy of Military Medical Sciences, Changchun, 130122, China.
authors.forename: Ye
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing, 100101, China.
authors.forename: Limin
authors.initials: L
authors.lastname: Yang
authors.affiliation: Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing, 100101, China.
authors.forename: Hongren
authors.initials: H
authors.lastname: Qu
authors.affiliation: Beijing Center for Animal Disease Control and Prevention Chinese Veterinary Medical Association of Animal Clinic Branch, Beijing, 102629, China.
authors.forename: Jingyi
authors.initials: J
authors.lastname: Zhao
authors.affiliation: Laboratory of Epidemiology and Key Laboratory of Jilin Province for Zoonosis Prevention and Control, Veterinary Research Institute, Academy of Military Medical Sciences, Changchun, 130122, China.
authors.forename: Rongliang
authors.initials: R
authors.lastname: Hu
authors.affiliation: Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing, 100101, China. lj418@163.com.|State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Harbin, 150001, China. lj418@163.com.
authors.forename: Jing
authors.initials: J
authors.lastname: Li
authors.affiliation: Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing, 100101, China. liuwj@im.ac.cn.|University of Chinese Academy of Sciences, Beijing, 100049, China. liuwj@im.ac.cn.
authors.forename: Wenjun
authors.initials: W
authors.lastname: Liu
mesh_terms: D000276:Adjuvants, Immunologic / Q000494:pharmacology*; D000818:Animals; D057134:Antibodies, Neutralizing / Q000097:blood; D000914:Antibodies, Viral / Q000097:blood / Q000276:immunology; D000956:Antigens, Viral / Q000235:genetics / Q000276:immunology; D060326:Chemistry Techniques, Synthetic; D004285:Dogs; D000939:Epitopes / Q000276:immunology; D005260:Female; D006023:Glycoproteins / Q000235:genetics / Q000276:immunology; D006360:Heat-Shock Proteins / Q000276:immunology* / Q000494:pharmacology; D000071497:Immunogenicity, Vaccine; D051379:Mice; D008807:Mice, Inbred BALB C; D011817:Rabbits; D011818:Rabies / Q000276:immunology* / Q000517:prevention & control / Q000662:veterinary / Q000821:virology; D011819:Rabies Vaccines / Q000276:immunology*; D011820:Rabies virus / Q000235:genetics / Q000276:immunology*; D011897:Random Allocation; D011994:Recombinant Proteins / Q000235:genetics / Q000276:immunology; D022223:Vaccines, Subunit / Q000737:chemistry / Q000276:immunology*; D014759:Viral Envelope Proteins / Q000235:genetics / Q000276:immunology
chemical_list: D000276:Adjuvants, Immunologic; D057134:Antibodies, Neutralizing; D000914:Antibodies, Viral; D000956:Antigens, Viral; D000939:Epitopes; D006023:Glycoproteins; D006360:Heat-Shock Proteins; D011819:Rabies Vaccines; D011994:Recombinant Proteins; D022223:Vaccines, Subunit; D014759:Viral Envelope Proteins; C064951:glycoprotein G, Rabies virus
keywords: Gp96; immunogenicity evaluation; multi-epitope-based vaccine; rabies virus