FLAVIVIRUS DNA VACCINE EFFICACY STUDIES IN NHPS

该子项目是利用 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。列出的机构是 研究中心，而研究中心不一定是研究者所在的机构。 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，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;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病毒（DEN-1、DEN-2、DEN-3和DEN-4）。除YF、JE和TBE外，没有疫苗可用于预防人类的其他黄病毒感染。 待测候选疫苗先前已在远交小鼠模型、几种禽类和马中显示出良好的耐受性，并且在所有年龄的接种小鼠、禽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新型候选疫苗在非人灵长类动物中抗JEV、WNV、YF和DEN 1-4攻击的安全性、免疫原性和保护效力。 本研究的结果将为下一研究阶段提供必要的数据，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.