Improved Vaccines for Rift Valley Fever Virus

描述（由申请人提供）：裂谷热病毒（RVFV）， NIAID a类病原体，是一种蚊媒布尼亚病毒，可通过气溶胶途径传播，在感染者中引起出血热、脑炎或视网膜炎。疫苗是控制裂谷热病毒最有效的手段，然而，目前还没有FDA批准的裂谷热病毒疫苗。因此，我们的研究小组，包括来自四所不同大学的具有疫苗开发、免疫调节和RVFV生物学专业知识的个人，已经开发并进行了两种基于甲病毒复制子颗粒或DNA疫苗的RVFV疫苗的初步分析，这些疫苗分别表达与C3d分子佐剂相关的RVFV糖蛋白的分泌形式。我们建议在小鼠模型中对这些疫苗进行详细的分析，包括单独的疫苗和启动-增强组合疫苗，以测试它们诱导抗裂谷热病毒保护性免疫反应的能力。该分析将包括与基于灭活RVFV和减毒活疫苗株MP-12的两种经典RVFV疫苗策略进行正面比较。这些研究将显著增强我们对抗裂谷热病毒免疫反应的理解，旨在确定能够迅速引发持久抗裂谷热病毒免疫的疫苗接种策略，最终目标是开发一种可用于人类的候选裂谷热病毒疫苗。

DESCRIPTION (provided by applicant): Rift Valley fever virus (RVFV), a NIAID Category A pathogen, is a mosquito borne bunyavirus that can be spread by the aerosol route and cause hemorrhagic fever, encephalitis, or retinitis in infected humans. Vaccines represent the most effective means of controlling RVFV, however, no FDA approved RVFV vaccines exist. Therefore, our research group, which includes individuals at four different Universities with expertise in vaccine development, immune modulation, and RVFV biology, has developed and performed preliminary analysis of two RVFV vaccines based on either alphavirus replicon particles or DNA vaccines expressing secreted forms of the RVFV glycoproteins linked to the C3d molecular adjuvant. We propose to perform a detailed analysis of these vaccines both individually and in prime-boost combination to test their ability to induce protective anti-RVFV immune responses in a mouse model. This analysis will include head-to-head comparisons with two classical RVFV vaccine strategies based on inactivated RVFV and the live attenuated vaccine strain, MP-12. These studies, which will significantly enhance our understanding of anti-RVFV immune responses, are designed to identify vaccination strategies that will rapidly elicit durable anti-RVFV immunity, with the ultimate goal of developing a candidate RVFV vaccine that can be taken forward for human use. PUBLIC HEALTH RELEVANCE: Rift Valley fever virus (RVFV) is a NIAID Category A pathogen that represents an emerging disease threat to countries in both the developing and developed world. Though vaccination represents an important means of controlling RVFV, there are currently no FDA approved RVFV vaccines for human use. Therefore, we propose to test two promising vaccination strategies for their ability to rapidly elicit long lived protective anti-RVFV immune responses. In addition to the development of promising new RVFV vaccines, these studies will also fundamentally advance our overall understanding anti-RVFV antibody and T cells responses, which will be useful for moving these or other vaccines forward for human use.