Natural Killer cells as effectors of vaccine-induced immunity

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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.