title: Malaria vaccine candidate: design of a multivalent subunit α-helical coiled coil poly-epitope.
abstract: A new strategy for the rapid identification of new malaria antigens based on protein structural motifs was previously described. We identified and evaluated the malaria vaccine potential of fragments of several malaria antigens containing α-helical coiled coil protein motifs. By taking advantage of the relatively short size of these structural fragments, we constructed different poly-epitopes in which 3 or 4 of these segments were joined together via a non-immunogenic linker. Only peptides that are targets of human antibodies with anti-parasite in vitro biological activities were incorporated. One of the constructs, P181, was well recognized by sera and peripheral blood mononuclear cells (PBMC) of adults living in malaria-endemic areas. Affinity purified antigen-specific human antibodies and sera from P181-immunized mice recognised native proteins on malaria-infected erythrocytes in both immunofluorescence and western blot assays. In addition, specific antibodies inhibited parasite development in an antibody dependent cellular inhibition (ADCI) assay. Naturally induced antigen-specific human antibodies were at high titers and associated with clinical protection from malaria in longitudinal follow-up studies in Senegal.
authors.affiliation: Centre Hospitalier Universitaire Vaudois CHUV, Lausanne, Switzerland.
authors.forename: Sope
authors.initials: S
authors.lastname: Olugbile
authors.forename: Viviane
authors.initials: V
authors.lastname: Villard
authors.forename: Sylvie
authors.initials: S
authors.lastname: Bertholet
authors.forename: Ali
authors.initials: A
authors.lastname: Jafarshad
authors.forename: Caroline
authors.initials: C
authors.lastname: Kulangara
authors.forename: Christian
authors.initials: C
authors.lastname: Roussilhon
authors.forename: Geraldine
authors.initials: G
authors.lastname: Frank
authors.forename: George W
authors.initials: GW
authors.lastname: Agak
authors.forename: Ingrid
authors.initials: I
authors.lastname: Felger
authors.forename: Issa
authors.initials: I
authors.lastname: Nebie
authors.forename: Karidia
authors.initials: K
authors.lastname: Konate
authors.forename: Andrey V
authors.initials: AV
authors.lastname: Kajava
authors.forename: Peter
authors.initials: P
authors.lastname: Schuck
authors.forename: Pierre
authors.initials: P
authors.lastname: Druilhe
authors.forename: François
authors.initials: F
authors.lastname: Spertini
authors.forename: Giampietro
authors.initials: G
authors.lastname: Corradin
mesh_terms: D000818:Animals; D000913:Antibodies, Protozoan / Q000097:blood / Q000276:immunology; D000953:Antigens, Protozoan / Q000737:chemistry* / Q000276:immunology*; D000939:Epitopes / Q000737:chemistry* / Q000276:immunology*; D005500:Follow-Up Studies; D006801:Humans; D007106:Immune Sera / Q000276:immunology; D008137:Longitudinal Studies; D008288:Malaria / Q000276:immunology / Q000517:prevention & control; D017780:Malaria Vaccines / Q000737:chemistry* / Q000276:immunology*; D051379:Mice; D008809:Mice, Inbred C3H; D008813:Mice, Inbred ICR; D010455:Peptides / Q000737:chemistry / Q000276:immunology; D010963:Plasmodium falciparum / Q000276:immunology; D017433:Protein Structure, Secondary; D012675:Senegal; D013329:Structure-Activity Relationship; D013601:T-Lymphocytes / Q000276:immunology
chemical_list: D000913:Antibodies, Protozoan; D000953:Antigens, Protozoan; D000939:Epitopes; D007106:Immune Sera; D017780:Malaria Vaccines; D010455:Peptides