Niu Yange, Liu Ye, Yang Limin, Qu Hongren, Zhao Jingyi, Hu Rongliang, Li Jing, Liu Wenjun
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.
Virol Sin. 2016 Apr;31(2):168-75. doi: 10.1007/s12250-016-3734-4. Epub 2016 Apr 6.
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.
狂犬病是一种人畜共患病，在全球导致超过55000人死亡，每年造成至少5亿美元的损失。目前可用的狂犬病疫苗主要是灭活疫苗和减毒疫苗，这些疫苗与动物的临床疾病有关。因此，迫切需要一种具有高安全性和有效性的狂犬病疫苗。肽疫苗以其低成本、简单的生产程序和高安全性而闻名。因此，在本研究中，我们检测了基于多表位的候选疫苗对狂犬病病毒的疗效。检测了各种肽诱导表位特异性反应的能力，并将具有最高抗原性和保守性的两种肽，即AR16和hPAB，与佐剂犬Gp96包被，用于制备疫苗。将这些肽制备成水包油（O/W）乳剂，制成三批二价疫苗产品。候选疫苗具有很高的安全性。在小鼠和比格犬首次免疫后第14天检测到病毒中和抗体，到第28天，小鼠体内达到5-6 IU/mL，比格犬体内达到7-9 IU/mL。在受到狂犬病病毒强毒株攻击的小鼠中，候选疫苗的保护效力约为70%-80%。因此，开发了一种以Gp96为佐剂的新型基于多表位的狂犬病疫苗，并在小鼠和犬中进行了验证。我们的结果表明，合成肽在开发新型狂犬病疫苗方面具有潜力。
