FLAVIVIRUS DNA VACCINE EFFICACY STUDIES IN NHPS

该子项目是利用该技术的众多研究子项目之一 资源由 NIH/NCRR 资助的中心拨款提供。子项目及 研究者 (PI) 可能已从 NIH 的另一个来源获得主要资金， 因此可以在其他 CRISP 条目中表示。列出的机构是 对于中心来说，它不一定是研究者的机构。 黄病毒感染的流行仍然是全世界主要的公共卫生问题。 超过 20 亿人面临感染这些病毒成员的风险，其中包括亚洲和澳大利亚的日本脑炎 (JE) 病毒；非洲和拉丁美洲的黄热病（YF）病毒；非洲、中欧和美洲的西尼罗河（WN）病毒；蜱传脑炎（TBE）复合病毒，包括欧洲和亚洲颞区的俄罗斯春夏脑炎（RSSE）和中欧脑炎（CEE）病毒；以及世界热带和亚热带地区的四种血清型登革热病毒（DEN-1、-2、-3 和 -4）。除 YF、JE 和 TBE 之外，尚无疫苗可预防人类其他黄病毒感染。 待测试的候选疫苗此前已在近交系小鼠模型、几种鸟类和马中显示出良好的耐受性，并且在所有年龄段的接种疫苗的小鼠、鸟类或马中均未观察到不良注射反应。初次免疫后血清中和抗体持续存在两年以上。 本研究的目的是评估针对 JEV、WNV、YF 和 DEN 1-4 攻击的新型候选疫苗在非人灵长类动物中的安全性、免疫原性和保护功效。 这项研究的结果将为下一阶段的研究提供重要数据，最终目标是支持人体临床试验。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Epidemics of flavivirus infections continue to be a major public health concern worldwide. More than two billion people are at risk of being infected with members of these viruses, including Japanese encephalitis (JE) virus in Asia and Australia; yellow fever (YF) virus in Africa and Latin America; West Nile (WN) virus in Africa Central Europe and America; tick-borne encephalitis (TBE) complex viruses, including Russian spring summer encephalitis (RSSE) and Central European encephalitis (CEE) viruses in the temporal regions of Europe and Asia; and four serotypes of dengue (DEN-1, -2, -3, and -4) viruses in the tropical and subtropical regions of the world. With the exceptions of YF, JE and TBE, vaccines are not available to prevent other flavivirus infections in humans. The vaccine candidates to be tested have previously been shown in outbred mice model, several avian species and horses to be well-tolerated, and no undesired injection reaction was observed in all ages of vaccinated mice, birds or horses. Serum neutralizing antibodies persisted for more than two years after primary immunization. The objective of this study is to assess the safety, immunogenicity and protective efficacy of novel vaccine candidates against JEV, WNV, YF and DEN 1-4 challenge in nonhuman primates. The results of this study will provide essential data for next study phase with the final goal for supporting human clinical trials.