HIV and immunity to malaria

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In Africa, Plasmodium falciparum malaria and HIV infection are devastating health problems, and HIV makes malaria worse, especially in pregnancy. Recently, we showed why this may be. In pregnancy, antibodies to proteins expressed on the surface of malaria infected cells protect against malaria in the placenta. Levels of these antibodies were decreased by HIV infection, and lowest in women with AIDS. Both first-time and experienced mothers lacked antibody. Now we will investigate the function of these antibodies. They might block adhesion to placental receptors, decreasing parasite numbers in the placenta. Or they might coat infected red cells, making them targets for phagocytosis (eating) by macrophages (white blood cells). We will examine the effects of HIV on each process, to find out how reduced antibody might affect the pregnant woman. HIV also affects macrophages and related immune cells, monocytes and dendritic cells. We will study how HIV infection in these cells impairs the way they eat malaria cells, and whether it alters the way they become activated and produce infection-fighting proteins when they encounter malaria. Without these proteins, malaria may grow unchallenged. Using our new assays we will study these responses in African women. We will discover whether HIV also affects antibodies to proteins expressed by parasites infecting children, who are at highest risk of malaria. HIV particularly decreases development of antibody to new targets, so children with little malaria experience may lack antibodies to many different proteins. We will find out whether low levels of malaria antibody in children may be the reason why the get more severe malaria. By understanding how HIV affects malaria immunity, we can develop better ways to protect people at risk from malaria. These findings will also be important to work on malaria vaccines. If HIV infected people respond poorly to natural infection, they may also fail to respond to vaccines.