title: Plasmodium ookinete-secreted proteins secreted through a common micronemal pathway are targets of blocking malaria transmission.
abstract: The mosquito midgut ookinete stage of the malaria parasite, Plasmodium, possesses microneme secretory organelles that mediate locomotion and midgut wall egress to establish sporogonic stages and subsequent transmission. The purpose of this study was 2-fold: 1) to determine whether there exists a single micronemal population with respect to soluble and membrane-associated secreted proteins; and 2) to evaluate the ookinete micronemal proteins chitinase (PgCHT1), circumsporozoite and TRAP-related protein (CTRP), and von Willebrand factor A domain-related protein (WARP) as immunological targets eliciting sera-blocking malaria parasite infectivity to mosquitoes. Indirect immunofluorescence localization studies in Plasmodium gallinaceum using specific antisera showed that all three proteins are distributed intracellularly with a similar granular cytoplasmic appearance and with focal concentration of PgCHT1 and PgCTRP, but not PgWARP, at the ookinete apical end. Immunogold double-labeling electron microscopy, using antisera against the membrane-associated protein CTRP and the soluble WARP, showed that these two proteins co-localized to the same micronemal population. Within the microneme CTRP was associated peripherally at the microneme membrane, whereas PgCHT1 and WARP were diffuse within the micronemal lumen. Sera produced against Plasmodium falciparum WARP significantly reduced the infectivity of P. gallinaceum to Aedes aegypti and P. falciparum to Anopheles mosquitoes. Antisera against PgCTRP and PgCHT1 also significantly reduced the infectivity of P. gallinaceum for A. aegypti. These results support the concept that ookinete micronemal proteins may constitute a general class of malaria transmission-blocking vaccine candidates.
authors.affiliation: Division of Infectious Diseases, Department of Medicine, University of California, San Diego, La Jolla, California 92093-0640, USA.
authors.forename: Fengwu
authors.initials: F
authors.lastname: Li
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: Templeton
authors.forename: Vsevolod
authors.initials: V
authors.lastname: Popov
authors.forename: Jason E
authors.initials: JE
authors.lastname: Comer
authors.forename: Takafumi
authors.initials: T
authors.lastname: Tsuboi
authors.forename: Motomi
authors.initials: M
authors.lastname: Torii
authors.forename: Joseph M
authors.initials: JM
authors.lastname: Vinetz
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D015153:Blotting, Western; D002462:Cell Membrane / Q000378:metabolism; D002688:Chitinases / Q000378:metabolism; D009033:Culicidae; D003593:Cytoplasm / Q000378:metabolism; D018076:DNA, Complementary / Q000378:metabolism; D004591:Electrophoresis, Polyacrylamide Gel; D004797:Enzyme-Linked Immunosorbent Assay; D019084:Fluorescent Antibody Technique, Indirect; D007150:Immunohistochemistry; D008024:Ligands; D008288:Malaria / Q000635:transmission*; D008854:Microscopy, Electron; D008856:Microscopy, Fluorescence; D016253:Microscopy, Immunoelectron; D008969:Molecular Sequence Data; D010961:Plasmodium / Q000378:metabolism*; D010963:Plasmodium falciparum / Q000378:metabolism*; D011485:Protein Binding; D015800:Protozoan Proteins / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000378:metabolism; D011994:Recombinant Proteins / Q000737:chemistry; D017386:Sequence Homology, Amino Acid; D013045:Species Specificity
chemical_list: D018076:DNA, Complementary; D008024:Ligands; C120163:PbCTRP protein, Plasmodium; D015800:Protozoan Proteins; D011956:Receptors, Cell Surface; D011994:Recombinant Proteins; C434321:WARP protein, Plasmodium; D002688:Chitinases