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Principal Investigator: Patrick Duffy
Organization: NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES
Fiscal Year: 2024
Award: $800,611
Funding agency: National Institute of Allergy and Infectious Diseases
In FY2024, we reported human and animal studies to investigate malaria immunology and pathogenesis, and malaria vaccine development. Highlighted in this year’s summary are results from our publications.
Miotto O et al. Identification of complex Plasmodium falciparum genetic backgrounds circulating in Africa: a multi-country genomic epidemiology analysis. 2024. The Lancet Microbe. In press.
In consortium work led by Sanger Center UK scientists, we analyzed P. falciparum genomes from 21 African countries and identified a distinct cluster, named AF1, comprising ~1.2% of samples from 13 countries. AF1 parasites have a unique genetic background with many highly differentiated variants across most chromosomes, which are rarely seen outside this cluster. Despite their unique loci, AF1 parasites are genetically similar to local parasites outside these regions. AF1 parasites sharing up to 23 genomic regions were found across Africa, even 7,000 km apart. We introduced the term "cryptotype" to describe this complex, widespread genetic background hidden by local genomic regions. Most AF1 variants are functionally related, involving genes in the MSP1 complex and others related to red blood cell interactions. We hypothesize that these may occupy a distinct ecological niche among circulating parasites, and will explore this in samples from our population studies.
Johnson Y, Shakri AR, Pond-Tor S, Jnawali A, Najrana T, Wu H, Badhai J, Alameh M-G, Weissman D, Kabyemela E, Duffy PE, Fried M, Kurtis J, Raj DK. Immunization with PfGBP130 generates antibodies that inhibit RBC invasion by P. falciparum parasites. 2024. Frontiers in Immunology. May 27; https://doi.org/10.3389/fimmu.2024.1350560
In collaborative work led by the Kurtis group at Brown, we used a whole proteome differential screening method and identified PfGBP130, a parasite protein recognized by antibodies from children resistant to P. falciparum infection. We formulated PfGBP130 as lipid-encapsulated mRNA, DNA plasmid, and recombinant protein-based immunogens. In mice, immunization with PfGBP130 as a DNA plasmid or lipid-encapsulated mRNA, induced antibodies that inhibited red blood cell invasion in vitro. We are advancing PfGBP130-A formulated as lipid-encapsulated mRNA for efficacy evaluation in non-human primates.
Terms: <0-11 years old><Africa><African><Animals><Antibodies><Antigens><Blood erythrocyte><Cell Communication><Cell Interaction><Cell-to-Cell Interaction><Child><Child Youth><Children (0-21)><Chromosomes><Complex><Country><Encapsulated><Erythrocytes><Erythrocytic><Genes><Genetic><Genomic Segment><Gestation><Host Factor><Host Factor Protein><Human><Immune response><Immunization><Immunological response><Immunology><In Vitro><Infection><Integration Host Factors><Invaded><Lipids><MSA-1><MSA-1 Protein><MSA1><MSA1 Protein><MSP-1><MSP1><Major Merozoite Surface Protein Precursor><Malaria><Malaria Vaccines><Malarial Vaccines><Marrow erythrocyte><Merozoite Surface Antigen 1><Merozoite Surface Protein 1><Messenger RNA><Methods><Mice><Mice Mammals><Microbe><Modern Man><Murine><Mus><Names><Outcome><P falciparum><P falciparum genome><P. falciparum><P. falciparum genome><P.falciparum><PFM-PSCP><PMMSA><Paludism><Parasitemia><Parasites><Pathogenesis><Plasmodium Infections><Plasmodium falciparum><Plasmodium falciparum Merozoite Precursor Surface Coat Protein><Plasmodium falciparum genome><Population Study><Pregnancy><Prevention><Proteins><Proteome><Publications><Recombinant Proteins><Red Blood Cells><Red Cell><Reporting><Resistance><Sampling><Scientific Publication><Scientist><Variant><Variation><Work><blood corpuscles><determine efficacy><develop a vaccine><develop vaccines><development of a vaccine><discover vaccines><efficacy analysis><efficacy assessment><efficacy determination><efficacy evaluation><efficacy examination><evaluate efficacy><examine efficacy><frontier><genome segment><genomic epidemiology><genomic region><host response><immune system response><immunogen><immunoresponse><inhibiting antibody><kids><mRNA><name><named><naming><non-human primate><nonhuman primate><offspring><parasaetemia><plasmid DNA><population-based study><population-level study><resistant><screening><screenings><studies of populations><study of the population><vaccine development><vaccine discovery><vaccines against malaria><youngster>