Manipulating immunity to Mycobacterium tuberculosis with novel vaccines and immunotherapeutics

用新型疫苗和免疫疗法控制结核分枝杆菌的免疫力

• 批准号: nhmrc : 402728
• 负责人: A/Pr James Triccas
• 金额: $ 34.99万
• 依托单位: The University of Sydney
• 依托单位国家: 澳大利亚
• 项目类别: NHMRC Project Grants
• 财政年份: 2006
• 资助国家: 澳大利亚
• 起止时间: 2006-01-01 至 2008-12-31
• 项目状态: 已结题
• 来源: https://researchdata.edu.au/manipulating-immunity-mycobacterium-vaccines-immunotherapeutics/80836
• 关键词: Manipulating; immunity; Mycobacterium; tuberculosis; novel

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.

结核病 (TB) 是一个巨大的世界健康问题，每年导致 200 万人死亡，估计世界上三分之一的人口感染了结核菌。感染该细菌且无法清除感染的人在以后的生活中患结核病的风险很高。结核病控制面临两大问题。首先，唯一可用于结核病的疫苗，即卡介苗，在预防这种疾病方面并不是很有效。我们不知道为什么卡介苗不是一种有效的疫苗，并且尚未完全了解实现最佳结核病保护所需的免疫反应类型。其次，目前治疗结核病的药物价格昂贵，治疗时间长，耐药性以惊人的速度增长。因此，迫切需要开发新的结核病疫苗和疗法。我们建议使用结核病感染的动物模型和先进的免疫学技术来比较结核病、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。还将研究增强肺部（结核感染的主要部位）免疫反应的新策略。这将涉及向肺部输送分子，以增加肺抗原呈递细胞的数量和有效性，这对于驱动正确类型的免疫反应以根除结核菌是必要的。增加肺部免疫力将用于增强卡介苗疫苗的效果，或作为杀死已感染者体内细菌的疗法。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最前沿。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策略将是一项重大医学突破，也是澳大利亚健康和医学研究的一项重大成就。