Immunogenicity of multi-epitope-based vaccine candidates administered with the adjuvant Gp96 against rabies  

作　　者：Yange Niu Ye Liu Limin Yang Hongren Qu Jingyi Zhao Rongliang Hu Jing Li Wenjun Liu 

机构地区：[1]Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, ChineseAcademy of Sciences, Beijing 100101, China [2]University of Chinese Academy of Sciences, Beijing 100049, China [3]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 [4]Beijing Center for Animal Disease Control and Prevention Chinese Veterinary Medical Association of Animal Clinic Branch, Beijing 102629, China [5]State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Harbin 150001, China

出　　处：《Virologica Sinica》2016年第2期168-175,共8页中国病毒学（英文版）

基　　金：supported by grants from the Special Fund for Agro-scientific Research in the Public Interest(201103032);the Fund of State Key Laboratory of Veterinary Biotechnology(SKLVBF201614);the National High Technology Research and Development Program of China(2015BAD11B02);Key Research Program of the Chinese Academy of Sciences(KSZD-EW-Z-005-001);the Special Fund for Chinese Academy of Sciences(CZBZX-1);WJL is the principal investigator of the NSFC Innovative Research Group(Grant No.81321063)

摘　　要：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 h PAB, were coated with adjuvant canineGp96 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/m L in mice and 7–9 IU/m L 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.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.

关 键 词：rabies virus multi-epitope-based vaccine immunogenicity evaluation GP96 

分 类 号：S852.4[农业科学—基础兽医学]