The worldwide AIDS pandemic is largely caused by one HIV strain called HIV-1, which after a variable length of time leads to AIDS and death in most infected people. There is a second HIV strain called HIV-2, which is mostly found in West Africa. This virus behaves quite differently from HIV-1: some HIV-2-infeceted people develop AIDS just as if they had HIV-1 but others, as many as 80%, have a normal lifespan and die of old age instead. We want to see if the immune response to the virus is different in these two groups of HIV-2-infected people, which may give useful clues about how to develop an HIV vaccine. We will be looking predominantly at cells in the blood called cytotoxic (or killer) lymphocytes because these cells have the ability to recognise and destroy HIV-infected cells.

MRC, Gambia unit is extending its research activities and impact in the region by developing research network with regional research institutions. MRC has enabled the support of these networks through external grant funding that primarily assist to empower these local institutions in building skills and capacity in order to embark on collaborative research and joint clinical trials. A consortium called WAPHIR (West Africa Platform for HIV Intervention Research -2010-2014) funded by GHRI/IDRC is created between MRC, the Laboratoire Bacteriologie-Virologie (LBV) of University Cheikh Anta Dio (UCAD) of Senegal and the Institute of Public Health Laboratory and Research/Bandim Health Project (INASA/BHP) of Guinea Bissau. It is embarking on Capacity strengthening through work packages that include a unified HIV cohort resource database network; clinical trial support and training; laboratory resource management and skill training; postgraduate training; network and communication training. Individual institutional cohort data resources from partners of the consortium are migrated into a centralised network server and training for the operation of the unified system was carried out, making a significant contribution towards the establishment of a regional HIV platform for supporting clinical trials and intervention research. Another network called WANETAM and WANETAM plus (West African Network for TB AIDS and Malaria 2009-2013) are funded By EDCTP and comprised of wider regional partnership (Burkina Faso, The Gambia, Ghana, Guinea Bissau, Mali, Nigeria, and Senegal). This network is building expertise in clinical trials for HIV, TB and Malaria. Research has started for HIV-2 pathogenesis in the network.

Mycobacterium africanum causes up to half of TB in West Africa. It is closely related to regular M. tuberculosis, but we have identified some important differences. One of these is that a new diagnostic test does not perform well in people infected with M. africanum. This test is based on the protein ESAT-6, which is also used in a new generation TB vaccine. Another difference is that HIV infected people are even more susceptible to infection with M. africanum than with M. tuberculosis. Thirdly, people who were exposed to M. africanum are less likely to develop TB than those exposed to M. tuberculosis.||We now propose to study the bacterial genes in more detail, in an attempt to pinpoint the causes for the differences. Ultimately we hope our findings on genetic differences may assist in optimization of diagnostic tests and perhaps with the design of new vaccine candidates.

Despite the availability of a vaccine measles kills about half a million children a year. Many of these victims are young African children living in crowded towns and cities who are intensely exposed to measles before 9 months of age when the usual measles vaccines are given. Earlier vaccination is not recommended as protective proteins (antibodies) derived from the mother neutralize and inactivate the live vaccine. However, the Edmonston-Zagreb strain of measles vaccine can evoke these neutralizing antibodies. Thus we are conducting a trial of this vaccine given in two doses to Gambian infants at 4 and 9 months of age. The comparison or control group will be children given a single dose of the vaccine at 9 months of age. The protective responses generated by one or two doses of the vaccine will be measured and compared between the two groups, and the safety of early measles vaccination will be monitored.If this initial small scale trial is successful the two dose strategy will be tried in a field site in Guinea-Bissau to determine whether it protects against measles disease. If this proves true the two dose regimen will be recommended for use in Africa or other parts of the world where measles is common.

Natural infection with many viruses results in the production of antibodies which help clear the virus and protect us from subsequent reinfection. Eliciting such a response is the basis of many effective vaccines, but unfortunately little is understood about protective antibody responses in HIV, which has hindered HIV vaccine design. Despite sharing many similarities with HIV-1, most patients with HIV-2 do not develop AIDS (although a minority do) and the reasons for this are not entirely clear. This project proposes to compare neutralizing antibody responses in HIV-1 and HIV-2 infection and explore whether stronger responses are found in HIV-2 infected patients who do not progress to AIDS, when compared to HIV-2 progressors and HIV-1 patients.||Early studies also suggested that HIV-2 antibodies could render HIV-1 non-functional and although some previous studies claimed HIV-2 infected individuals may be protected against subsequent HIV-1 infection, the majority suggest no protection or even an increased risk of acquiring HIV-1 superinfection. We therefore propose to compare HIV-1 cross-neutralizing antibody responses and enhancing antibody responses in HIV-2 patients who go on to acquire HIV-1 superinfection, with those who have remained HIV-2 mono-infected despite possible exposure to HIV-1.||Such information could provide vital clues to how the HIV surface interacts with antibodies and the importance of eliciting an antibody response in future HIV vaccines.