title: Structure-activity-based design of a synthetic malaria peptide eliciting sporozoite inhibitory antibodies in a virosomal formulation.
abstract: The circumsporozoite protein (CSP) of Plasmodium falciparum is a leading candidate antigen for inclusion in a malaria subunit vaccine. We describe here the design of a conformationally constrained synthetic peptide, designated UK-39, which has structural and antigenic similarity to the NPNA-repeat region of native CSP. NMR studies on the antigen support the presence of helical turn-like structures within consecutive NPNA motifs in aqueous solution. Intramuscular delivery of UK-39 to mice and rabbits on the surface of reconstituted influenza virosomes elicited high titers of sporozoite crossreactive antibodies. Influenza virus proteins were crucially important for the immunostimulatory activity of the virosome-based antigen delivery system, as a liposomal formulation of UK-39 was not immunogenic. IgG antibodies elicited by UK-39 inhibited invasion of hepatocytes by P. falciparum sporozoites, but not by antigenically distinct P. yoelii sporozoites. Our approach to optimized virosome-formulated synthetic peptide vaccines should be generally applicable for other infectious and noninfectious diseases.
authors.affiliation: Molecular Immunology, Swiss Tropical Institute, CH-4002 Basel, Switzerland.
authors.forename: Shinji L
authors.initials: SL
authors.lastname: Okitsu
authors.forename: Ursula
authors.initials: U
authors.lastname: Kienzl
authors.forename: Kerstin
authors.initials: K
authors.lastname: Moehle
authors.forename: Olivier
authors.initials: O
authors.lastname: Silvie
authors.forename: Elisabetta
authors.initials: E
authors.lastname: Peduzzi
authors.forename: Markus S
authors.initials: MS
authors.lastname: Mueller
authors.forename: Robert W
authors.initials: RW
authors.lastname: Sauerwein
authors.forename: Hugues
authors.initials: H
authors.lastname: Matile
authors.forename: Rinaldo
authors.initials: R
authors.lastname: Zurbriggen
authors.forename: Dominique
authors.initials: D
authors.lastname: Mazier
authors.forename: John A
authors.initials: JA
authors.lastname: Robinson
authors.forename: Gerd
authors.initials: G
authors.lastname: Pluschke
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D000911:Antibodies, Monoclonal / Q000737:chemistry / Q000276:immunology; D000913:Antibodies, Protozoan / Q000096:biosynthesis* / Q000276:immunology*; D002626:Chemistry, Pharmaceutical; D003429:Cross Reactions; D015195:Drug Design; D004591:Electrophoresis, Polyacrylamide Gel; D004797:Enzyme-Linked Immunosorbent Assay; D005455:Fluorescent Antibody Technique; D006825:Hybridomas / Q000276:immunology; D009682:Magnetic Resonance Spectroscopy; D017780:Malaria Vaccines / Q000737:chemistry* / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008958:Models, Molecular; D008969:Molecular Sequence Data; D010714:Phosphatidylethanolamines / Q000737:chemistry; D010963:Plasmodium falciparum / Q000276:immunology / Q000472:pathogenicity; D010967:Plasmodium yoelii / Q000276:immunology / Q000472:pathogenicity; D015800:Protozoan Proteins / Q000737:chemistry* / Q000276:immunology*; D011817:Rabbits; D013329:Structure-Activity Relationship; D022701:Virosomes / Q000737:chemistry*
chemical_list: D000911:Antibodies, Monoclonal; D000913:Antibodies, Protozoan; D017780:Malaria Vaccines; D010714:Phosphatidylethanolamines; D015800:Protozoan Proteins; D022701:Virosomes; C041595:circumsporozoite protein, Protozoan