Vaccination for LASSA FEVER

描述：(申请人提供)在西非流行的拉萨病毒， 每年感染10万-30万人，导致5000-10000人死亡，并离开 约有3万人患有神经性耳聋等后遗症。的总目标是 这项拨款提案是为了了解对LASSA的保护性免疫反应 病毒，从而使我们有能力开发一种针对拉沙热的疫苗。拉萨 病毒是生物安全级别4(BSL4)的代理，由此施加的限制 事实严重阻碍了我们研究代理人的能力。不过， 疫苗研究是在近十年前在豚鼠和 并清楚地表明，保护性免疫可以被授予 对抗这种疾病。然而，疫苗的保护成分(S)诱导 豁免权尚未确定。我们现在处于更加强大的地位，可以 评估保护组件，并在我们的实验中进行评估 求婚。我们的团队对新出现的病毒有广泛的经验， 尤其是拉萨病毒。此外，我们还拥有多年的经验， 设计针对旧大陆禽流感病毒的疫苗。我们将使用的构造 将利用最近的进展，极大地增强诱导的免疫反应 通过DNA疫苗，优化T细胞(CD8+和CD4+)的诱导，以及 抗体。拉沙热只有两个可靠的挑战模型， 豚鼠和灵长类动物。斯克里普斯的合作者将首先评估 疫苗对豚鼠免疫动物的免疫原性 被送往USAMRIID进行活病毒挑战试验。第二年，这项研究 然后我们将转到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)的特征是具有Mamu I等位基因，以便 在一个模型中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，接种疫苗的猴子将 将被转移到USAMRIID，在那里将根据 彼得·B·贾林博士的监督，以及所有合作者将 现场共同努力，确保对以下方面的反应进行详尽的评估 个别灵长类动物。这些研究预计将导致 确定一种可在人体上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.