title: Generation of Plasmodium falciparum parasite-inhibitory antibodies by immunization with recombinantly-expressed CyRPA.
abstract: BACKGROUND
  The pathogenesis of malaria is primarily associated with blood-stage infection and there is strong evidence that antibodies specific for parasite blood-stage antigens can control parasitaemia. This provides a strong rationale for incorporation of asexual blood-stage antigen components into an effective multivalent malaria subunit vaccine. On the basis of available genome-wide transcriptomic and proteomic data, previously uncharacterized Plasmodium falciparum open reading frames were screened for new blood stage vaccine candidates. This has led to the identification of the cysteine-rich protective antigen (PfCyRPA), which forms together with PfRH5 and PfRipr a multiprotein complex that is crucial for erythrocyte invasion.
  
  
  METHODS
  Glycosylated and non-glycosylated variants of recombinant PfCyRPA were expressed and produced as secreted protein in mammalian cells. Adjuvanted formulations of purified PfCyRPA were tested to assess whether they can effectively elicit parasite inhibitory antibodies, and to investigate whether or not the glycosylation status affects antibody binding. For this purpose, two sets of PfCyRPA-specific mouse monoclonal antibodies (mAbs) have been raised and evaluated for functional activity.
  
  
  RESULTS
  Generated PfCyRPA-specific mAbs, irrespective of the immunogen's glycosylation status, showed substantial parasite in vitro growth-inhibitory activity due to inhibition of erythrocyte invasion by merozoites. Furthermore, passive immunization experiments in P. falciparum infected NOD-scid IL2Rγ (null) mice engrafted with human erythrocytes demonstrated potent in vivo growth-inhibitory activity of generated mAbs.
  
  
  CONCLUSIONS
  Recombinantly expressed PfCyRPA tested as adjuvanted vaccine formulations in mice elicited antibodies that significantly inhibit P. falciparum asexual blood stage parasite growth both in vitro and in vivo. These findings render PfCyRPA a promising blood-stage candidate antigen for inclusion into a multicomponent malaria subunit vaccine.
authors.affiliation: Medical Parasitology and Infection Biology Department, Swiss Tropical and Public Health Institute, Basel, Switzerland.|University of Basel, Basel, Switzerland.
authors.forename: Paola
authors.initials: P
authors.lastname: Favuzza
authors.affiliation: Medical Parasitology and Infection Biology Department, Swiss Tropical and Public Health Institute, Basel, Switzerland.|University of Basel, Basel, Switzerland.
authors.forename: Simon
authors.initials: S
authors.lastname: Blaser
authors.affiliation: Medical Parasitology and Infection Biology Department, Swiss Tropical and Public Health Institute, Basel, Switzerland.|University of Basel, Basel, Switzerland.
authors.forename: Anita M
authors.initials: AM
authors.lastname: Dreyer
authors.affiliation: Medical Parasitology and Infection Biology Department, Swiss Tropical and Public Health Institute, Basel, Switzerland.|University of Basel, Basel, Switzerland.
authors.forename: Guy
authors.initials: G
authors.lastname: Riccio
authors.affiliation: Medical Parasitology and Infection Biology Department, Swiss Tropical and Public Health Institute, Basel, Switzerland.|University of Basel, Basel, Switzerland.
authors.forename: Marco
authors.initials: M
authors.lastname: Tamborrini
authors.affiliation: Roche Pharmaceutical Research & Early Development, Small Molecule Research, Roche Innovation Center Basel, F. Hoffmann-La Roche Ltd., Basel, Switzerland.
authors.forename: Ralf
authors.initials: R
authors.lastname: Thoma
authors.affiliation: Roche Pharmaceutical Research & Early Development, Small Molecule Research, Roche Innovation Center Basel, F. Hoffmann-La Roche Ltd., Basel, Switzerland.
authors.forename: Hugues
authors.initials: H
authors.lastname: Matile
authors.affiliation: Medical Parasitology and Infection Biology Department, Swiss Tropical and Public Health Institute, Basel, Switzerland. gerd.pluschke@unibas.ch.|University of Basel, Basel, Switzerland. gerd.pluschke@unibas.ch.
authors.forename: Gerd
authors.initials: G
authors.lastname: Pluschke
mesh_terms: D000276:Adjuvants, Immunologic / Q000008:administration & dosage; D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology* / Q000302:isolation & purification; D000913:Antibodies, Protozoan / Q000276:immunology* / Q000302:isolation & purification; D000953:Antigens, Protozoan / Q000008:administration & dosage / Q000276:immunology*; D017780:Malaria Vaccines / Q000008:administration & dosage / Q000276:immunology*; D051379:Mice; D010963:Plasmodium falciparum / Q000254:growth & development* / Q000276:immunology*; D014614:Vaccines, Synthetic / Q000008:administration & dosage / Q000276:immunology
chemical_list: D000276:Adjuvants, Immunologic; D000911:Antibodies, Monoclonal; D000913:Antibodies, Protozoan; D000953:Antigens, Protozoan; D017780:Malaria Vaccines; D014614:Vaccines, Synthetic
keywords: Blood-stage vaccines; CyRPA; Erythrocyte invasion; Malaria