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Volume 31 Issue 2
April 2016
    Citation: Yange Niu, Ye Liu, Limin Yang, Hongren Qu, Jingyi Zhao, Rongliang Hu, Jing Li, Wenjun Liu. Immunogenicity of multi-epitope-based vaccine candidates administered with the adjuvant Gp96 against rabies .VIROLOGICA SINICA, 2016, 31(2) : 168-175.  http://dx.doi.org/10.1007/s12250-016-3734-4
    shu

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

    • 1.

      Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy 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

    • Corresponding author: Jing Li, lj418@163.com
      Wenjun Liu, liuwj@im.ac.cn
    • Received Date: 29 January 2016
      Accepted Date: 16 March 2016
      Published Date: 06 April 2016
      Available online: 01 April 2016
    • 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 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/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.
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      Immunogenicity of multi-epitope-based vaccine candidates administered with the adjuvant Gp96 against rabies

        Corresponding author: Jing Li, lj418@163.com
        Corresponding author: Wenjun Liu, liuwj@im.ac.cn
      • 1. Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy 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
      • Received Date: 29 January 2016
      • Accepted Date: 16 March 2016
      • Published Date: 06 April 2016

      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 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/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.

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