Vaccination for LASSA FEVER

描述：（由申请人提供）拉沙病毒，在西非流行， 每年感染10万至30万人，造成5000至10000人死亡， 约三万人有神经性耳聋等后遗症。的总目标 这项拨款提案是为了了解对拉沙的保护性免疫反应， 因此，我们有能力开发出一种针对拉沙热的疫苗。拉沙 病毒是生物安全4级（BSL 4）制剂， 这严重阻碍了我们研究这种病原体的能力然而，尽管如此， 大约十年前，在豚鼠身上进行了疫苗研究， 灵长类动物，并清楚地表明，保护性免疫可以赋予 对抗这种疾病。然而，疫苗诱导的保护性成分 免疫力没有被发现。我们现在处于更有利的地位， 评估保护组件，并将在实验中这样做，我们 求婚我们的团队对新出现的病毒有着广泛的经验， 尤其是拉沙病毒此外，我们还拥有多年的经验， 设计对抗旧大陆沙粒病毒的疫苗我们将使用的结构 将利用最近的进展，大大提高免疫反应诱导 通过DNA疫苗，优化T细胞（CD8+和CD4+）的诱导， 抗体的拉沙热只有两种可靠的挑战模型， 豚鼠和灵长类动物。斯克里普斯的合作者将首先评估 疫苗在豚鼠中的免疫原性， 送往USAMRIID进行活病毒挑战试验。第二年，研究 然后我们将转向休斯顿的灵长类动物模型，在那里我们将使用恒河猴 猕猴（印度起源）的特征在于MAMU I等位基因， 评估灵长类动物的免疫反应， 人类对相同病毒抗原的反应。最后，接种疫苗的猴子 转移至USAMRIID，在该研究中将根据 Peter B博士的监督。耶林，在那里所有的合作者将 联合收割机现场工作，确保对 灵长类动物的个体这些研究预计将导致 确定一种可在人体中进行测试的候选拉沙疫苗。

DESCRIPTION: (Provided by Applicant) Lassa virus, endemic in West Africa, infects 100,000-300,000 people annually, killing 5,000-10,000, and leaving about 30,000 with residual sequelae such as nerve deafness. The overall goal of this grant proposal is to understand the protective immune response to Lassa virus, thus positioning us to develop a vaccine against Lassa fever. Lassa virus is a Biosafety level 4 (BSL4) agent, and the constraints imposed by this fact have significantly impeded our ability to study the agent. Nevertheless, vaccine studies were carried out almost a decade ago, in guinea pigs and primates, and showed clearly that protective immunity could be conferred against this disease. However, the protective component(s) of vaccine-induced immunity were not identified. We are now in a much stronger position to evaluate the protective components, and shall do so in the experiments we propose. Our group has extensive experience with emerging viruses in general, and Lassa virus in particular. In addition we have many years of experience in designing vaccines against Old World arenaviruses. The constructs we will use will exploit recent advances that greatly enhance the immune responses induced by DNA vaccines, optimizing the induction of T cells (CD8+ and CD4+), and antibodies. There are only two reliable challenge models for Lassa fever, guinea pigs and primates. The Scripps collaborators will first evaluate the immunogenicity of the vaccines in guinea pigs with immunized animals also being sent to USAMRIID for live virus challenge trials. In the second year the study will then move to the primate models in Houston, where we will use rhesus macaques (Indian origin) characterized in the MAMU I allele in order to evaluate the immune response in primates in a model that closely parallels the human responses to the same viral antigens. Finally the vaccinated monkeys will be moved to USAMRIID where challenge studies will be performed under the supervision of Dr. Peter B. Jahrling, and where all the collaborators will combine efforts on site to ensure an exhaustive evaluation of the responses of the individual primates. These studies are expected to lead to the identification of a candidate Lassa vaccine that can be tested in humans.