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Crystal clear: visualizing the intervention mechanism of the PD-1/PD-L1 interaction by two cancer therapeutic monoclonal antibodies
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  • 分类:S858.292[农业科学—临床兽医学;农业科学—兽医学;农业科学—畜牧兽医] Q78[生物学—分子生物学]
  • 作者机构:[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 ofAnimal Clinic Branch, Beijing 102629, China, [5]State Key Laboratory of Veterinary Biotechnology, Harbin Veterinary Research Institute, ChineseAcademy of Agricultural Sciences, Harbin 150001, China
  • 相关基金: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)
中文摘要:

狂犬病, zoonotic 疾病,原因 > 55,000 人的死亡全球性并且每年在损失导致至少 5 亿美元。当前可得到的狂犬病疫苗主要被使失去活性并且稀释了疫苗,它在动物与临床的疾病被连接了。因此,有高安全和功效的一支狂犬病疫苗着急地被需要。肽疫苗以他们的低花费的、简单生产过程和高安全著名。在这研究,因此,我们对狂犬病病毒检验了 multi-epitope-based 疫苗候选人的功效。各种各样的肽的能力被检验导致 epitope 特定的回答,并且拥有了最高的 antigenicity 和保存的二肽,即, AR16 和 hPAB,与辅助 canine-Gp96 是涂的并且过去常准备疫苗。肽在水(O/W ) 里作为油的乳剂被准备创造二原子价的疫苗的产品的三批。疫苗的候选人拥有了高安全。病毒抵销抗体在老鼠和猎兔犬在在第一免疫以后的日子 14 上被检测,在白天到达在老鼠的 5-6 IU/mL 和在猎兔犬的 7-9 IU/mL 28。疫苗的候选人的保护的功效关于在狂犬病病毒的剧毒的紧张质问的老鼠的 70%-80% 。因此,有 Gp96 的一支新奇 multi-epitope-based 狂犬病疫苗在老鼠和狗作为一个助手被开发并且验证。我们的结果对狂犬病为新奇疫苗的发展建议那条合成的肽抓住诺言。

英文摘要:

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 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.

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