Differences in Humoral Immune Response to Plasmodium falciparum in HIV-1-Infected and HIV-Exposed/Uninfected Ugandan Children

Award amount: 40,000.00

HIV and malaria are two of the most prevalent infections facing the world today, with the largest impact seen in sub-Saharan Africa. Although there are studies describing humoral immune responses in HIV or malaria, little is known about the immunologic impact of co-infection. The specific aims of this study are to investigate the differences in the humoral immune response to Plasmodium falciparum in children with and without HIV-1- infection. We hypothesize that HIV-1-infection, specifically with low CD4 T cell percentage, increases the risk of malaria infection by decreasing production and affinity of protective antibodies. We will test this hypothesis by measuring responses to two erythrocytic-stage P. falciparum antigens that have been previously associated with protection, apical membrane antigen-1 (AMA1) and merozoite surface protein 3 (MSP3). Furthermore, based on recent evidence that HIV leads to expansion of a dysfunctional B cell population, we will test the hypothesis that co-infection leads to expansion of dysfunctional B cells and a decreased ability to differentiate into antigen-specific antibody-secreting cells. In order to test our hypotheses in this one-year study, we will leverage longitudinal patient samples from an existing, well-characterized cohort of Ugandan children. Antibody responses and affinity to AMA1 and MSP3 over time will be measured in HIV-1-infected and uninfected children using ELISA. Frequencies of dysfunctional B cells will be analyzed by flow cytometry and the ability of B cells to differentiate into P. falciparum -specific antibody secreting cells will be assessed by ELISPOT. The results of these studies will provide new insight on the impact of HIV-1 on malaria and development of humoral immunity in children.