Statens Serum Institut, Department of Infectious Disease Immunology, Artillerivej 5, 2300 Copenhagen S, Denmark.
Statens Serum Institut, Department of Infectious Disease Immunology, Artillerivej 5, 2300 Copenhagen S, Denmark.
Trends Immunol. 2014 Aug;35(8):387-95. doi: 10.1016/j.it.2014.04.006. Epub 2014 May 27.
The vaccine discovery paradigm in tuberculosis (TB) has been to mimic the natural immune response to infection. With an emphasis on interferon (IFN)-γ as the main protective cytokine, researchers have selected dominant antigens and administered them in delivery systems to promote strong T helper (Th)1 responses. However, the Bacillus Calmette-Guérin (BCG) vaccine is a strong inducer of Th1 cells, yet has limited protection in adults, and further boosting by the Modified-Vaccinia-Ankara (MVA)85A vaccine failed to enhance efficacy in a clinical trial. We review the current understanding of host-pathogen interactions in TB infection and propose that rather than boosting Th1 responses, we should focus on understanding protective immune responses that are lacking or insufficiently promoted by BCG that can intervene at critical stages of the TB life cycle.
结核病（TB）疫苗研发的范式是模拟机体对感染的天然免疫反应。研究人员强调干扰素（IFN）-γ作为主要的保护性细胞因子，选择优势抗原并将其递送至载体中以促进强烈的辅助性 T 细胞（Th）1 反应。然而，卡介苗（BCG）是 Th1 细胞的强力诱导剂，但在成人中的保护作用有限，改良型牛型结核分枝杆菌（MVA）85A 疫苗进一步增强其效力的临床试验也未能成功。我们回顾了宿主-病原体相互作用在结核感染中的当前认识，并提出，我们不应仅仅关注增强 Th1 反应，而应着眼于理解缺乏或不足以被 BCG 促进的保护性免疫反应，这些反应可在结核生命周期的关键阶段发挥作用。
