Improved Vaccines for Rift Valley Fever Virus

描述（由申请方提供）：裂谷热病毒（RVFV）是一种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，并在受感染人群中引起出血热、脑炎或视网膜炎。疫苗代表了控制RVFV的最有效手段，然而，不存在FDA批准的RVFV疫苗。因此，我们的研究小组，其中包括在疫苗开发，免疫调节，和RVFV生物学专业知识的四个不同的大学的个人，已经开发和进行了两个RVFV疫苗的初步分析，基于甲病毒复制子颗粒或DNA疫苗表达的RVFV糖蛋白的分泌形式连接到C3 d分子佐剂。我们建议对这些疫苗单独和初免-加强组合进行详细分析，以测试它们在小鼠模型中诱导保护性抗RVFV免疫应答的能力。该分析将包括与基于灭活RVFV和活减毒疫苗株MP-12的两种经典RVFV疫苗策略的头对头比较。这些研究将显著增强我们对抗RVFV免疫应答的理解，旨在确定将快速引发持久抗RVFV免疫的疫苗接种策略，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NIAID A类病原体，代表了对发展中国家和发达国家的新兴疾病威胁。尽管疫苗接种代表了控制RVFV的重要手段，但目前没有FDA批准的用于人的RVFV疫苗。因此，我们建议测试两种有前途的疫苗接种策略，以快速引发长期保护性抗RVFV免疫应答的能力。除了开发有前景的新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细胞应答的整体理解，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.