Natural Killer cells as effectors of vaccine-induced immunity

疫苗接种是减少许多传染病全球负担的最可持续和最具成本效益的方法。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，制造针对这些感染的有效疫苗非常困难。目前，测试这些疫苗的唯一方法是进行临床试验，让数百或数千人接种疫苗，然后等待看他们是否会感染。如果疫苗不起作用呢？如果不能奏效——就像最近几种疟疾、艾滋病毒和结核病疫苗的情况一样——那么就花费了大量的时间和金钱，但是我们并没有更接近于了解哪里出了问题。加快疫苗开发进程的一种方法是确定？保护的相关因素？换句话说，识别免疫反应，当免疫反应出现时，就能很好地表明这个人受到了保护。对于许多疫苗来说，血液中存在针对疫苗有机体的抗体提供了该人受到保护的证据，但对于疟疾、艾滋病毒和结核病等疾病，抗体是保护的不良指示，需要采取其他应对措施。本研究的目的是评估潜在的新相关保护的预测价值，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ifn - γ和杀死受感染细胞对IL-2作出反应的能力。我们怀疑这些反应与保护的关系比现有的标记要好。我们将通过比较接种前后的免疫反应来测试这一点，看看是否诱导了T细胞和NK细胞的反应，看看接种后反应持续了多长时间，看看这些反应的存在是否是保护所必需的，是否是保护的一个很好的指标。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型肝炎疫苗，在预防肝炎和肝癌方面非常有效。我们的初步数据表明，这种疫苗可以诱导产生IL-2的T细胞和产生ifn - γ的NK细胞，我们现在想看看这些反应是否与长期预防乙型肝炎感染相关。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.