TUBERCULOSIS VACCINE DEVELOPMENT

世界人口的三分之一感染了结核分枝杆菌（TB）。每年有900多万人患病，与结核病相关的死亡人数超过150万。它是感染艾滋病毒的成年人死亡的主要原因之一。特别是，结核病在肺中生存和复制。即使在接种过卡介苗的成年人中，通常也需要2至3周的时间才能让肺部的T细胞（抗结核病的主要免疫臂）产生反应。世卫组织制定了疫苗策略，通过在感染部位（肺粘膜）激发强效T细胞反应，减轻或可能预防结核感染后的发病机制。经证明，雾化递送抗原是一种有效的肺部免疫方案；VRC在非人灵长类动物模型中具有丰富的这种递送经验，并显示出通过这种方式对流感和SIV发病机制具有保护作用的强大免疫反应。此外，VRC数据显示，在非人类灵长类动物中，非常强的T细胞反应在肺部保持相对稳定一年或更长时间。基于这些数据，VRC将评估一种假设，即与标准卡介苗接种相比，将结核病抗原气溶胶递送到肺部将提供更快速和有效的t细胞反应，从而减少发病机制和/或减轻结核病感染。为了验证这一假设，将在合适的动物模型中进行详细的研究。将研究菌种选择、结核挑战菌株、挑战递送途径和其他变量。

One third of the world's population is infected with Mycobacterium tuberculosis (TB). Annually, more than 9 million become sick, and there are more than 1.5 million TB related deaths. It is one of the leading causes of death in HIV-infected adults. In particular, TB resides and replicates in the lung. Even in BCG vaccinated adults, it normally takes 2 to 3 weeks for T cells, the primary arm of immunity against TB, to respond in the lung. The VRC has developed vaccine strategies to attenuate or possibly prevent pathogenesis following infection with TB by eliciting potent T cell responses at the site of infection, the lung mucosa. Aerosol delivery of antigens has proven to be a potent immunization scheme in the lung; the VRC has extensive experience with such delivery in the nonhuman primate model and has shown strong immune responses protective against influenza and SIV pathogenesis by such a modality. In addition, VRC data show that very strong T cell responses are elicited that remain relatively stable in the lung for a year or more in nonhuman primates. Based on these data, the VRC will evaluate the hypothesis that aerosol delivery of TB antigens to the lung will provide more rapid and potent T-cell responses compared to standard BCG vaccination, resulting in decreased pathogenesis and/or attenuated infection by TB. To test this hypothesis, detailed research studies in a suitable animal model will be performed. The choice of species, TB challenge strain, challenge delivery route, and other variables will be studied.