FLAVIVIRUS DNA VACCINE EFFICACY STUDIES IN NHPS

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 黄病毒感染的流行仍然是世界范围内的一个主要公共卫生问题。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病毒；非洲和拉丁美洲的黄热病病毒；非洲、中欧和美洲的西尼罗河病毒；欧亚时间区域的森林脑炎(TBE)复合体病毒，包括俄罗斯春夏脑炎(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(登革热-1、-2、-3和-4)。除流行性感冒、乙型乙型脑炎和乙型脑炎外，没有疫苗可用于预防人类感染其他黄病毒。待测试的候选疫苗此前已在近交系小鼠模型中显示，几种禽类和马具有良好的耐受性，在接种疫苗的所有年龄的小鼠、鸟或马中均未观察到不良注射反应。初免后血清中和抗体持续两年以上。本研究的目的是评估新型疫苗候选疫苗在非人灵长类动物中的安全性、免疫原性和对乙脑、西尼罗河病毒、YF和登革热1-4攻击的保护效果。这项研究的结果将为下一个研究阶段提供必要的数据，最终目标是支持人类临床试验。

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.