Malaria caused by Plasmodium falciparum remains a major public health threat. Over 225 million cases of malaria occur annually among the worlds poorest populations, claiming the lives of nearly a million children each year in Africa alone. The widespread implementation of malaria control interventions such as artemisinin-based combination therapy and insecticide-treated bed nets is hampered by the poor health-care infrastructure of many malaria-endemic countries. Moreover, P. falciparum has proven adept at acquiring and rapidly spreading resistance to antimalarial drugs, and vector control is constantly threatened by the inevitability of the emergence of insecticide-resistant mosquitoes. Ultimately, a key tool for the control, elimination, or even eradication of malaria is an effective vaccine. The development of a highly effective malaria vaccine has been hindered in part by a poor understanding of the interaction between P. falciparum and the human immune system. Importantly, protective immunity to malaria can be acquired after repeated P. falciparum infections but wanes rapidly in the absence of ongoing exposure. The quality of the innate and adaptive immune responses that ultimately confers this protection and the mechanisms that underlie their inefficient acquisition and rapid loss are largely unknown. Our objective is to aid malaria vaccine development by addressing these critical knowledge gaps. To this end, we apply recent advances in immunology and genomics-based technology to rigorously conducted longitudinal cohort studies in malaria-endemic areas to deepen our understanding of the interaction between P. falciparum and the human immune system and to define molecular and cellular signatures of malaria immunity. In FY 2013 we continued to pursue five main objectives: 1) obtain high quality clinical data and biospecimens from ongoing longitudinal cohort studies in Mali in which exposure to P. falciparum infection and protection against malaria are reliably assessed, 2) determine the antigen specificity, function, kinetics and cellular basis of the antibody response to P. falciparum, 3) define the mechanisms by which P. falciparum-induced inflammation is regulated, 4) identify a molecular signature of immunity to malaria through systems biology approaches, and 5) determine the relationship between persistent asymptomatic P. falciparum infection and malaria risk, and elucidate the host and parasite factors that underlie this phenomenon. The large cohort studies we conduct in Mali are made possible through a close collaboration with an experienced team of clinicians and scientists at the University of Sciences, Techniques &Technologies of Bamako (USTTB). To expand the scope of our work and to maximize the knowledge gained from our cohort studies in Mali, we collaborate with experts in parasite biology, basic immunology, genomics and computational biology. For example, we have an ongoing collaboration with the J. Craig Venter Institute to incorporate powerful sequencing-based technologies into the analysis of our cohort studies in Mali. Genomic and transcriptomic signatures of both the host and parasite that correlate with malaria clinical outcomes are yielding new hypotheses regarding the biological mechanisms through which malaria immunity is induced by natural P. falciparum infection. This and other ongoing projects are contributing to a more comprehensive understanding of the acquisition and maintenance of immunity to malaria, and also providing insights into the mechanisms at play in human immune responses to infectious diseases more generally.

Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
Zip Code
Liu, Eugene W; Skinner, Jeff; Tran, Tuan M et al. (2018) Protein-Specific Features Associated with Variability in Human Antibody Responses to Plasmodium falciparum Malaria Antigens. Am J Trop Med Hyg 98:57-66
Ouattara, Amed; Tran, Tuan M; Doumbo, Safiatou et al. (2018) Extent and Dynamics of Polymorphism in the Malaria Vaccine Candidate Plasmodium falciparum Reticulocyte-Binding Protein Homologue-5 in Kalifabougou, Mali. Am J Trop Med Hyg 99:43-50
Miura, Kazutoyo; Crompton, Peter D (2018) What goes around comes around: modeling malaria transmission from humans back to mosquitos. J Clin Invest 128:1264-1266
Arora, Gunjan; Hart, Geoffrey T; Manzella-Lapeira, Javier et al. (2018) NK cells inhibit Plasmodium falciparum growth in red blood cells via antibody-dependent cellular cytotoxicity. Elife 7:
Wendel, Ben S; He, Chenfeng; Qu, Mingjuan et al. (2017) Accurate immune repertoire sequencing reveals malaria infection driven antibody lineage diversification in young children. Nat Commun 8:531
Portugal, Silvia; Obeng-Adjei, Nyamekye; Moir, Susan et al. (2017) Atypical memory B cells in human chronic infectious diseases: An interim report. Cell Immunol 321:18-25
Bustamante, Leyla Y; Powell, Gareth T; Lin, Yen-Chun et al. (2017) Synergistic malaria vaccine combinations identified by systematic antigen screening. Proc Natl Acad Sci U S A 114:12045-12050
Pieper, Kathrin; Tan, Joshua; Piccoli, Luca et al. (2017) Public antibodies to malaria antigens generated by two LAIR1 insertion modalities. Nature 548:597-601
Mogeni, Polycarp; Omedo, Irene; Nyundo, Christopher et al. (2017) Effect of transmission intensity on hotspots and micro-epidemiology of malaria in sub-Saharan Africa. BMC Med 15:121
Hansen, Diana S; Obeng-Adjei, Nyamekye; Ly, Ann et al. (2017) Emerging concepts in T follicular helper cell responses to malaria. Int J Parasitol 47:105-110

Showing the most recent 10 out of 54 publications