Simultaneous parenteral and pulmonary immunisation against tuberculosis

每年有200万人死于结核病感染，这是一个日益严重的问题，因为艾滋病毒/艾滋病使个人极易感染，而且耐抗生素结核分枝杆菌菌株正在出现。目前的结核病疫苗卡介苗仅部分有效，因此开发更好的疫苗是一项紧急的卫生保健优先事项。到目前为止，大多数新的结核病疫苗都是在卡介苗之后接种的，以增强卡介苗提供的弱免疫力。这被称为初始增强免疫。然而，越来越清楚的是，初级增强免疫可能不足以有效地控制结核病。在这个项目中，我们将建立一种新的替代免疫策略，称为同步免疫（SIM）。我们已经证明，通过注射一种结核病疫苗，同时向小鼠肺部喷洒另一种疫苗是非常有效的。肺部疫苗建立局部免疫，在感染后立即对抗结核病感染，而注射疫苗的效果较慢，但两者结合起来非常有效。我们现在想在老鼠身上测试几种不同的SIM制度，以找到最有效的一种并测试其安全性。我们还将研究不同的白细胞如何结合起来保护肺部免受结核病的侵害，以便在未来制造更有效的疫苗。与此同时，我们将研究感染结核病的人，以开发更好的测试来评估对结核病的免疫力。这将有助于在人体中测试新的免疫程序，包括SIM。一种更好的结核病疫苗将对人类的健康有重大好处，而且还可以用来控制牛结核病，这种疾病目前在英国广泛传播，并造成相当大的经济损失。

Two million individuals die each year from tuberculosis infection, which is an increasing problem because HIV/AIDS makes individuals highly susceptible and because antibiotic resistant strains of Mycobacterium tuberculosis are appearing. The present tuberculosis vaccine, BCG, is only partially effective, so development of a better vaccine is an urgent health care priority. Up to now, most new tuberculosis vaccines have been designed to be given after BCG, in order to boost the weak immunity provided by BCG. This is called prime boost immunisation. However, it is becoming clear that prime boost immunisation may not be sufficiently effective to control tuberculosis.In this project we will establish an alternative novel immunisation strategy called Simultaneous Immunisation (SIM). We have already shown that giving one tuberculosis vaccine by injection and simultaneously spraying another into the lungs is highly effective in mice. The lung vaccine establishes local immunity, which combats tuberculosis infection immediately after infection, and the injected vaccine has a slower effect, but the two work very effectively together. We now want to test several different SIM regimes in mice to find the most effective one and test its safety. We will also study how different white cells combine to protect the lungs against tuberculosis, in order to make even more effective vaccines in the future. At the same time we will study humans infected with tuberculosis to develop better tests to assess immunity to tuberculosis. This will help in testing new immunisation procedures, including SIM, in man. A better tuberculosis vaccine will have major health benefits for humans and can also be used to control bovine tuberculosis, which is currently widespread in the UK and causes considerable economic losses.