Manipulating immunity to Mycobacterium tuberculosis with novel vaccines and immunotherapeutics

结核病（TB）是一个巨大的世界卫生问题，每年有200万人死亡，估计世界人口的三分之一感染了结核杆菌。感染了这种细菌而不能清除感染的人在以后的生活中患结核病的风险很大。结核病的控制面临两个主要问题。首先，唯一可用的结核病疫苗卡介苗在预防该病方面不是很有效。我们不知道为什么卡介苗不是一种有效的疫苗，也不完全了解实现对结核病最佳保护所需的免疫反应类型。第二，目前用于治疗结核病的药物价格昂贵，治疗时间长，耐药性正在以惊人的速度增加。因此，迫切需要开发新的结核病疫苗和治疗方法。我们建议使用结核感染动物模型和复杂的免疫学技术来比较结核、卡介苗和我们实验室开发的新一代疫苗产生的免疫反应。这将使我们能够确定疫苗的关键特征，从而有效、持久地预防结核病感染。还将研究增加肺部（结核感染的主要部位）免疫反应的新策略。这将涉及到通过肺输送分子来增加肺抗原提呈细胞的数量和有效性，这是驱动正确类型的免疫反应以根除结核杆菌所必需的。增强肺部免疫力将被用来增强卡介苗的效果，或者作为一种杀死已经感染的人体内细菌的治疗方法。这是一个具有国际竞争力的项目，我们的团队处于这项研究工作的前沿。开发预防结核病的新疫苗或治疗已确定的结核病感染的新战略将是一项重大医学突破，是澳大利亚卫生和医学研究的一项重大成就。

Tuberculosis (TB) is an enormous world health problem with 2 million deaths per year and an estimated one third of the world s population infected with the TB bacterium. People who become infected with the bacterium and cannot clear the infection are at great risk of developing TB later in life. Control of TB is confronted with two major problems. First, the only vaccine available for TB, known as BCG, is not very effective at preventing the disease. We do not know why BCG is not an effective vaccine and the type of immune response required to achieve optimal protection against TB is not fully understood. Second, the drugs currently used to treat TB are expensive, treatment times are long and drug resistance is increasing at an alarming rate. Therefore there is an urgent need to develop new vaccines and therapies against TB. We propose to use animal models of TB infection and sophisticated immunological techniques to compare immune responses generated by TB, BCG and new generation vaccines developed in our laboratory. This will allow us to identify the key features of a vaccine that results in effective, long-lasting protection against TB infection. Novel strategies to increase the immune response in the lung, the main site of TB infection, will also be examined. This will involve pulmonary delivery of molecules that increase the number and effectiveness of lung antigen presenting cells, which are necessary to drive the right type of immune response to eradicate the TB bacterium. Increasing lung immunity will be used to either boost the effect of the BCG vaccine, or as a therapy to kill the bacterium in those already infected. This is an internationally competitive project and our team is at the forefront of this research effort. The development of new vaccines to prevent TB or new strategies to treat established TB infection would be a major medical breakthrough and a represent a significant achievement for Australian health and medical research.