HIV
Currently, an estimated 33 million people are living with HIV-1 infection. Despite progress in expanding access to antiretroviral therapy (ART), less than one third of people who need treatment are receiving it. The overall aim of Dr Lucy Dorrell's research programme is to develop immunotherapy for HIV-1 infection which will reduce dependence on ART. Since virus-specific CD8+ T cell responses are a key determinant of the rate at which people with HIV-1 infection progress to AIDS, wh her team are investigating whether these responses can be strengthened or modulated by vaccination during HAART and whether this will lead to enhanced control of HIV-1 replication. They have shown that vaccination of chronically infected patients with DNA- and modified vaccinia virus Ankara (MVA)-vectored vaccines expressing an HIV-1 immunogen boosts HIV-specific T cell responses.a They are extending these clinical studies in order to address several questions which are critical to the development of effective immunotherapy: (i) by how much CD8+ T cell responses to HIV-1 need to be boosted in order to reduce viral load set-point in chronic infection?; (ii) are other factors such as the kinetics or quality of the response more important than its magnitude?; (iii) do specific activation phenotypes correlate with antiviral functions in CD8+ T cells?; (iv) is the expansion of HIV-1-specific CD8+ T cells inhibited by immunosuppressive responses induced by the virus?; (v) are these immunosuppressive pathways amenable to therapeutic intervention?
