TUBERCULOSIS VACCINE DEVELOPMENT

世界上三分之一的人口感染了结核分枝杆菌（TB）。每年有900多万人患病，150多万人死于结核病。它是感染艾滋病毒的成年人死亡的主要原因之一。特别地，TB在肺中驻留和复制。即使在接种卡介苗的成年人中，T细胞（抗结核免疫的主要分支）通常也需要2至3周才能在肺部产生反应。VRC已经开发了疫苗策略，通过在感染部位（肺粘膜）引发有效的T细胞应答来减弱或可能预防TB感染后的发病机制。已证明抗原的气溶胶递送是肺中的有效免疫方案; VRC在非人灵长类动物模型中具有这种递送的丰富经验，并且通过这种方式显示出针对流感和SIV发病机制的强免疫应答保护性。此外，VRC数据显示，在非人灵长类动物中，非常强的T细胞应答在肺中保持相对稳定一年或更长时间。 基于这些数据，VRC将评估以下假设：与标准BCG疫苗接种相比，将TB抗原气溶胶递送至肺部将提供更快速和更有效的T细胞应答，从而导致发病率降低和/或TB感染减弱。 为了检验这一假设，将在合适的动物模型中进行详细的研究。 将研究种属、TB攻毒株、攻毒递送途径和其他变量的选择。

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.