The main interest of our group is in understanding immunity to virus infection, with a particular focus on how immune responses modify the outcome of HIV and other viral infections. The main aim is to define correlates of protective immunity against HIV infection that would help in the design of vaccines to prevent infection. An effective HIV vaccine is desperately needed, particularly in the developing world where the greatest burden of HIV disease occurs.
We work closely with clinicians and epidemiologists to study immune responses in clinical cohorts in Kenya, West Africa, Zimbabwe and China, as well as in the UK. In Kenya we focus on infants born to infected mothers, both infected and uninfected, to try and understand why the clinical outcome in HIV-infected children is so much worse than in adults, particularly in sub-Saharan Africa (before the widespread use of early anti-retroviral therapy). In Zimbabwe we are studying a recently-identified group of older children and adolescents with long-term HIV-1 infection who were not diagnosed in early life, partly to understand the mechanisms underlying long-term survival following vertical infection but also to understand the basis of the clinical complications reported in a high proportion of these HIV-infected adolescents. In China we study a village cohort of former plasma donors who became infected with what appear to be very closely related HIV strains whilst taking part in an illegal plasma donation scheme in the mid-1990s: the similar infecting viruses in this cohort magnifies the impact of host genetic and immune factors on viral evolution and clinical outcome.
Our group has a long-standing interest in the second strain of HIV, HIV-2, which is found predominantly in W. Africa and leads to a high proportion of long-term non-progressors (LTNPs), even though progressors with HIV-2 infection are clinically indistinguishable from people with progressive HIV-1 infection. Our data suggest that the most important differences between progressors and non-progressors with HIV-2 infection lie in their immune response to the virus, with LTNPs having much stronger and more potent T-cell responses that are associated with viral control. We are currently investigating how these protective responses are generated in some people but not in others, as well as looking at the role of a host restriction factor, TRIM5 alpha, in mediating viral control in HIV-2 infection.