title: Epitope analysis of the malaria surface antigen pfs48/45 identifies a subdomain that elicits transmission blocking antibodies.
abstract: Pfs48/45, a member of a Plasmodium-specific protein family, displays conformation-dependent epitopes and is an important target for malaria transmission-blocking (TB) immunity. To design a recombinant Pfs48/45-based TB vaccine, we analyzed the conformational TB epitopes of Pfs48/45. The Pfs48/45 protein was found to consist of a C-terminal six-cysteine module recognized by anti-epitope I antibodies, a middle four-cysteine module recognized by anti-epitopes IIb and III, and an N-terminal module recognized by anti-epitope V antibodies. Refolding assays identified that a fragment of 10 cysteines (10C), comprising the middle four-cysteine and the C-terminal six-cysteine modules, possesses superior refolding capacity. The refolded and partially purified 10C conformer elicited antibodies in mice that targeted at least two of the TB epitopes (I and III). The induced antibodies could block the fertilization of Plasmodium falciparum gametes in vivo in a concentration-dependent manner. Our results provide important insight into the structural organization of the Pfs48/45 protein and experimental support for a Pfs48/45-based subunit vaccine.
authors.affiliation: Department of Molecular Biology, NCMLS, Radboud University Nijmegen, PO Box 9101, 6500 HB Nijmegen, The Netherlands.
authors.forename: Nikolay
authors.initials: N
authors.lastname: Outchkourov
authors.forename: Adriaan
authors.initials: A
authors.lastname: Vermunt
authors.forename: Josephine
authors.initials: J
authors.lastname: Jansen
authors.forename: Anita
authors.initials: A
authors.lastname: Kaan
authors.forename: Will
authors.initials: W
authors.lastname: Roeffen
authors.forename: Karina
authors.initials: K
authors.lastname: Teelen
authors.forename: Edwin
authors.initials: E
authors.lastname: Lasonder
authors.forename: Anneke
authors.initials: A
authors.lastname: Braks
authors.forename: Marga
authors.initials: M
authors.lastname: van de Vegte-Bolmer
authors.forename: Li Yan
authors.initials: LY
authors.lastname: Qiu
authors.forename: Robert
authors.initials: R
authors.lastname: Sauerwein
authors.forename: Hendrik G
authors.initials: HG
authors.lastname: Stunnenberg
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D000913:Antibodies, Protozoan / Q000096:biosynthesis*; D000953:Antigens, Protozoan / Q000737:chemistry / Q000276:immunology*; D004797:Enzyme-Linked Immunosorbent Assay; D000939:Epitopes / Q000737:chemistry / Q000276:immunology*; D005260:Female; D019084:Fluorescent Antibody Technique, Indirect; D008562:Membrane Glycoproteins / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D015800:Protozoan Proteins / Q000276:immunology*; D017386:Sequence Homology, Amino Acid
chemical_list: D000913:Antibodies, Protozoan; D000953:Antigens, Protozoan; D000939:Epitopes; D008562:Membrane Glycoproteins; D015800:Protozoan Proteins; C084847:pfs48-45 protein, Plasmodium falciparum