Improved Vaccines for Rift Valley Fever Virus

描述(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，可通过气雾剂路线传播，并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，然而，目前还没有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的在疫苗开发、免疫调节和RVFV生物学方面具有专业知识的个人，已经开发并进行了两种RVFV疫苗的初步分析，这两种疫苗是基于甲型病毒复制子颗粒或表达与C3d分子佐剂相连的RVFV糖蛋白的分泌形式的DNA疫苗。我们建议对这些疫苗单独和Prime-Boost组合进行详细分析，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。这项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疫苗策略进行面对面的比较。这些研究将显著提高我们对抗RVFV免疫反应的了解，旨在确定将迅速产生持久的抗RVFV免疫的疫苗接种策略，最终目标是开发一种可推进人类使用的候选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都是一种新出现的疾病威胁。虽然接种疫苗是控制RVFV的重要手段，但目前还没有FDA批准的供人类使用的RVFV疫苗。因此，我们建议测试两种有前景的疫苗接种策略，以测试它们快速诱导长期保护性抗RVFV免疫反应的能力。除了开发有希望的新RVFV疫苗外，这些研究还将从根本上促进我们对抗RVFV抗体和T细胞反应的全面了解，这将有助于推动这些或其他疫苗供人类使用。

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.