Improved Vaccines for Rift Valley Fever Virus

描述（由申请人提供）：裂谷热病毒 (RVFV) 是 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，在受感染的人类中引起出血热、脑炎或视网膜炎。疫苗是控制 RVFV 的最有效手段，但目前尚无 FDA 批准的 RVFV 疫苗。因此，我们的研究小组（包括来自四所不同大学、在疫苗开发、免疫调节和 RVFV 生物学方面拥有专业知识的个人）开发了两种 RVFV 疫苗，并进行了初步分析，这两种疫苗基于甲病毒复制子颗粒或表达与 C3d 分子佐剂相连的 RVFV 糖蛋白分泌形式的 DNA 疫苗。我们建议对这些疫苗进行单独和初免-加强组合的详细分析，以测试它们在小鼠模型中诱导保护性抗 RVFV 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 疫苗策略进行头对头比较。这些研究将显着增强我们对抗 RVFV 免疫反应的理解，旨在确定能够快速引发持久抗 RVFV 免疫力的疫苗接种策略，最终目标是开发可供人类使用的候选 RVFV 疫苗。 公共卫生相关性：裂谷热病毒 (RVFV) 是一种 NIAID A 类病原体，对发展中国家和发达国家来说都是一种新出现的疾病威胁。尽管疫苗接种是控制 RVFV 的重要手段，但目前尚无 FDA 批准的人类使用的 RVFV 疫苗。因此，我们建议测试两种有前景的疫苗接种策略，看看它们是否能够快速引发长期保护性抗 RVFV 免疫反应。除了开发有前景的新型 RVFV 疫苗外，这些研究还将从根本上推进我们对抗 RVFV 抗体和 T 细胞反应的整体了解，这将有助于推动这些或其他疫苗用于人类。

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.