Hepatitis C virus (HCV) infects over 170 million people in the world. Most individuals develop a chronic infection associated with progressive liver disease. While new drugs have recently been developed, they are very expensive and are not a treatment option for developing countries. In addition, there are some patients groups e.g. patients co-infected with HIV-1 that may not be as responsive to therapy. Drug resistant variants of the virus may also emerge. For all these reasons, there is an urgent need to develop a vaccine against HCV.
Our collaborators in Oxford are at the cutting-edge of translational medicine in terms of HCV vaccine design and are conducting human clinical trials to test new vaccines for their efficacy in healthy volunteers and HIV-1 infected patients. One arm of the current trial is taking place in St. James Hospital, Dublin.
In this project, we will investigate the potential of harnessing the innate immune system, in particular Natural Killer (NK) cells, to improve HCV immunogenicity during vaccination. We will investigate changes in NK cell activation, function and metabolism in response to HCV vaccination in healthy individuals and define how these correlate with protective adaptive immunity. We have preliminary evidence that supports activation of both NK cell cytokine production and cytotoxic functions during vaccination. By identifying a mechanism by which NK cells contribute to the development of adaptive immunity, we can target these specific functions in the next generation of vaccines.
Patients infected with HIV-1 are at high risk for co-infection with HCV. However, as their immune systems are already compromised, additional strategies e.g. targeting NK cells, may be particularly important to allow the development of adaptive immunity in response to vaccination.
In summary, NK cells may provide key immune targets for the next generation of HCV vaccines.
