title: Identification of GAPDH on the surface of Plasmodium sporozoites as a new candidate for targeting malaria liver invasion.
abstract: Malaria transmission begins when an infected mosquito delivers Plasmodium sporozoites into the skin. The sporozoite subsequently enters the circulation and infects the liver by preferentially traversing Kupffer cells, a macrophage-like component of the liver sinusoidal lining. By screening a phage display library, we previously identified a peptide designated P39 that binds to CD68 on the surface of Kupffer cells and blocks sporozoite traversal. In this study, we show that the P39 peptide is a structural mimic of glyceraldehyde 3-phosphate dehydrogenase (GAPDH) on the sporozoite surface and that GAPDH directly interacts with CD68 on the Kupffer cell surface. Importantly, an anti-P39 antibody significantly inhibits sporozoite liver invasion without cross-reacting with mammalian GAPDH. Therefore, Plasmodium-specific GAPDH epitopes may provide novel antigens for the development of a prehepatic vaccine.
authors.affiliation: Department of Molecular Microbiology and Immunology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD 21205 Malaria Research Institute, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD 21205.
authors.forename: Sung-Jae
authors.identifier: 0000-0003-0468-1723
authors.initials: SJ
authors.lastname: Cha
authors.affiliation: McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21205.
authors.forename: Min-Sik
authors.initials: MS
authors.lastname: Kim
authors.affiliation: McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21205.
authors.forename: Akhilesh
authors.identifier: 0000-0001-9943-6127
authors.initials: A
authors.lastname: Pandey
authors.affiliation: Department of Molecular Microbiology and Immunology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD 21205 Malaria Research Institute, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD 21205 mlorena@jhsph.edu.
authors.forename: Marcelo
authors.initials: M
authors.lastname: Jacobs-Lorena
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D000913:Antibodies, Protozoan / Q000276:immunology; D015703:Antigens, CD / Q000378:metabolism; D015214:Antigens, Differentiation, Myelomonocytic / Q000378:metabolism; D002460:Cell Line; D002462:Cell Membrane / Q000201:enzymology*; D017124:Conserved Sequence; D005987:Glyceraldehyde-3-Phosphate Dehydrogenases / Q000737:chemistry / Q000378:metabolism*; D006801:Humans; D007728:Kupffer Cells / Q000469:parasitology / Q000473:pathology; D008024:Ligands; D008099:Liver / Q000469:parasitology* / Q000473:pathology*; D008288:Malaria / Q000276:immunology / Q000469:parasitology*; D017780:Malaria Vaccines / Q000276:immunology; D018345:Mice, Knockout; D010455:Peptides / Q000737:chemistry / Q000276:immunology; D010962:Plasmodium berghei / Q000276:immunology / Q000472:pathogenicity*; D011485:Protein Binding; D051381:Rats; D034101:Sporozoites / Q000201:enzymology*; D000097382:CD68 Molecule
chemical_list: D000913:Antibodies, Protozoan; D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D005987:Glyceraldehyde-3-Phosphate Dehydrogenases; D008024:Ligands; D017780:Malaria Vaccines; D010455:Peptides; C067980:CD68 antigen, human; D000097382:CD68 Molecule