title: Passive immunoprotection of Plasmodium falciparum-infected mice designates the CyRPA as candidate malaria vaccine antigen.
abstract: An effective malaria vaccine could prove to be the most cost-effective and efficacious means of preventing severe disease and death from malaria. In an endeavor to identify novel vaccine targets, we tested predicted Plasmodium falciparum open reading frames for proteins that elicit parasite-inhibitory Abs. This has led to the identification of the cysteine-rich protective Ag (CyRPA). CyRPA is a cysteine-rich protein harboring a predicted signal sequence. The stage-specific expression of CyRPA in late schizonts resembles that of proteins known to be involved in merozoite invasion. Immunofluorescence staining localized CyRPA at the apex of merozoites. The entire protein is conserved as shown by sequencing of the CyRPA encoding gene from a diverse range of P. falciparum isolates. CyRPA-specific mAbs substantially inhibited parasite growth in vitro as well as in a P. falciparum animal model based on NOD-scid IL2Rγ(null) mice engrafted with human erythrocytes. In contrast to other P. falciparum mouse models, this system generated very consistent results and evinced a dose-response relationship and therefore represents an unprecedented in vivo model for quantitative comparison of the functional potencies of malaria-specific Abs. Our data suggest a role for CyRPA in erythrocyte invasion by the merozoite. Inhibition of merozoite invasion by CyRPA-specific mAbs in vitro and in vivo renders this protein a promising malaria asexual blood-stage vaccine candidate Ag.
authors.affiliation: Swiss Tropical and Public Health Institute, CH-4051 Basel, Switzerland.
authors.forename: Anita M
authors.initials: AM
authors.lastname: Dreyer
authors.forename: Hugues
authors.initials: H
authors.lastname: Matile
authors.forename: Petros
authors.initials: P
authors.lastname: Papastogiannidis
authors.forename: Jolanda
authors.initials: J
authors.lastname: Kamber
authors.forename: Paola
authors.initials: P
authors.lastname: Favuzza
authors.forename: Till S
authors.initials: TS
authors.lastname: Voss
authors.forename: Sergio
authors.initials: S
authors.lastname: Wittlin
authors.forename: Gerd
authors.initials: G
authors.lastname: Pluschke
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D000913:Antibodies, Protozoan / Q000276:immunology; D000953:Antigens, Protozoan / Q000235:genetics / Q000276:immunology*; D015153:Blotting, Western; D004797:Enzyme-Linked Immunosorbent Assay; D004912:Erythrocytes / Q000469:parasitology; D005434:Flow Cytometry; D005455:Fluorescent Antibody Technique; D057809:HEK293 Cells; D006801:Humans; D017780:Malaria Vaccines / Q000276:immunology*; D016778:Malaria, Falciparum / Q000517:prevention & control*; D052940:Merozoites / Q000276:immunology; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D008969:Molecular Sequence Data; D010963:Plasmodium falciparum / Q000235:genetics / Q000276:immunology / Q000472:pathogenicity; D015800:Protozoan Proteins / Q000235:genetics / Q000276:immunology*; D016415:Sequence Alignment; D020349:Surface Plasmon Resonance; D014162:Transfection
chemical_list: D000913:Antibodies, Protozoan; D000953:Antigens, Protozoan; C000622047:CyRPA protein, Plasmodium falciparum; D017780:Malaria Vaccines; D015800:Protozoan Proteins