Natural Killer cells as effectors of vaccine-induced immunity

接种疫苗是减轻全球许多传染病负担的最可持续和最具成本效益的方式。包括疟疾、艾滋病毒和结核病在内的许多感染迫切需要新的疫苗，但事实证明，很难制造出针对这些感染的有效疫苗。目前，测试这些疫苗的唯一方法是进行临床试验，让成百上千的人接种疫苗，然后等待，看看他们是否会感染。如果疫苗不起作用--就像最近几种疟疾、艾滋病毒和结核病疫苗的情况一样--那么我们已经花费了大量的时间和金钱，但我们还没有更深入地了解哪里出了问题。加快疫苗开发进程的一种方法是确定保护相关因素。换句话说，识别免疫反应，当存在时，是一个人受到保护的良好指标。对于许多疫苗，血液中存在的疫苗有机体抗体提供了个人受到保护的证据，但对于疟疾、艾滋病毒和结核病等疾病，抗体并不能很好地表明保护，需要其他反应。这项研究的目的是评估潜在的新的保护相关因素的预测价值，即称为T细胞的细胞产生称为IL-2的分子的能力，以及自然杀伤(NK)细胞通过产生干扰素-γ和杀死感染的细胞来响应IL-2的能力。我们怀疑，与现有标记相比，这些反应与保护的相关性更好。我们将通过比较接种前后的免疫反应来测试这一点，看看是否已经诱导了T细胞和NK细胞反应，看看这些反应在接种后持续了多长时间，以及这些反应的存在是否是保护所必需的，以及这些反应是否是保护的良好指标。这项工作的很大一部分将在西非冈比亚的MRC实验室进行。1984年，冈比亚引进了一种乙肝疫苗，在预防肝炎和肝癌方面非常有效。我们的初步数据表明，这种疫苗同时诱导产生IL-2的T细胞和产生干扰素-γ的NK细胞，我们现在想看看这些反应是否与预防乙肝感染的长期保护相关。如果是这样，我们将研究如何通过接种疫苗最有效地诱导这些反应。

Vaccination is the most sustainable and cost-effective way to reduce the global burden of many infectious diseases. New vaccines are urgently needed for many infections including malaria, HIV and TB but it has proven very difficult to make efficacious vaccines against these infections. Currently, the only way to test these vaccines is to carry out clinical trials where many hundreds or thousands of people are vaccinated and then wait to see if they become infected or not. If the vaccines don?t work - as has been the case recently for several malaria, HIV and TB vaccines - then a lot of time and money has been spent but we are no nearer to understanding what is going wrong. One way to speed up the process of vaccine development is to identify ?correlates of protection?. In other words, to identify immune responses which, when present, are good indicators that the person is protected. For many vaccines, the presence in the blood of antibodies to the vaccine organism provides evidence that the person is protected but, for diseases such as malaria, HIV and TB, antibodies are a poor indication of protection and other responses are required. The purpose of this research is to evaluate the predictive value of potential new correlates of protection, namely the ability of cells called T cells to make a molecule called IL-2 and the ability of natural killer (NK) cells to respond to IL-2 by making IFN-gamma and killing infected cells. We suspect that these responses correlate better with protection than do existing markers. We will test this by comparing immune responses before and after vaccination to see if T cell and NK cell responses have been induced, see how long the responses last after vaccination, and see if the presence of these responses is required for protection and is a good indicator of protection. A large part of this work will be carried out at the MRC Laboratories in The Gambia, West Africa. In 1984, a vaccine for hepatitis B was introduced in The Gambia and has been highly effective at preventing hepatitis and liver cancer. Our preliminary data indicate this vaccine induces both IL-2 producing T cells and IFN-gamma-producing NK cells and we now want to see if these responses are correlated with long term protection against hepatitis B infection. If so, we will investigate how these responses can be most efficiently induced by vaccination.