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Principal Investigator: Peter Crompton
Organization: NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES
Fiscal Year: 2020
Award: $2,359,843
Funding agency: National Institute of Allergy and Infectious Diseases
Malaria caused by Plasmodium falciparum remains a major public health threat. Over 225 million cases of malaria occur annually among the world's poorest populations, claiming the lives of approximately 500,000 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 poorly understood. Our objective is to inform 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, to define molecular and cellular signatures of malaria immunity and to identify potential malaria vaccine targets. In FY 2020 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, entomology, basic immunology, genomics and computational biology. These 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.
Terms: <0-11 years old><2019 novel coronavirus><2019-nCoV><Address><Africa><Anti-malarial drug resistance><Anti-malarial drug resistant><Antibodies><Antibody Response><Antigens><Antimalarial drug resistance><Antimalarial drug resistant><Area><Artemisinins><Beds><Biology><Child><Child Youth><Children (0-21)><Clinical Data><Cohort Studies><Collaborations><Combined Modality Therapy><Communicable Diseases><Computational Biology><Concurrent Studies><Country><Culicidae><Development><Drug Controls><Entomology><Exposure to><Falciparum Malaria><Genomics><Healthcare><Hu-mABs><Human><Immune><Immune response><Immune system><Immunes><Immunity><Immunological response><Immunology><Individual><Infection><Infectious Disease Pathway><Infectious Diseases><Infectious Disorder><Inflammation><Infrastructure><Insecticide Resistance><Insecticides><Intervention><Intervention Strategies><Kinetics><Knowledge><Long-term cohort study><Longitudinal cohort study><Longterm cohort study><Maintenance><Malaria><Malaria Vaccines><Malarial Vaccines><Mali><Modern Man><Molecular><Molecular Fingerprinting><Molecular Profiling><Mosquitoes><Multimodal Therapy><Multimodal Treatment><NIAID><National Institute of Allergy and Infectious Disease><P falciparum><P. falciparum><P.falciparum><Paludism><Parasites><Plasmodium Infections><Plasmodium falciparum><Plasmodium falciparum Malaria><Play><Population><Public Health><Risk><SARS-CoV-2><SARS-CoV2><SARS-associated coronavirus 2><SARS-coronavirus-2><SARS-related coronavirus 2><Science><Scientist><Severe acute respiratory syndrome coronavirus 2><Specificity><Systems Biology><Technology><Translating><Universities><Vaccines><Work><Wuhan coronavirus><acquired immunity><adaptive immune response><allergic/immunologic body system><allergic/immunologic organ system><anti-malarial resistance><antimalarial resistance><arteannuin><artemisinine><base><children><childrens'><combination therapy><combined modality treatment><combined treatment><computer biology><develop a vaccine><development of a vaccine><developmental><experience><health care><host response><humAbs><human mAbs><human monoclonal antibodies><human monoclonals><immunogen><immunoresponse><insecticide resistant><insight><interventional strategy><molecular profile><molecular signature><multi-modal therapy><multi-modal treatment><optimism><postiive attitude><qinghaosu><quing hau sau><quinghaosu><resistance to anti-malarial drug><resistance to antimalarial drug><resistant to anti-malarial drug><resistant to antimalarial drug><technology/technique><tool><vaccine development><vaccine formulation><vaccines against malaria><vector control><youngster>