title: A malaria vaccine that elicits in humans antibodies able to kill Plasmodium falciparum.
abstract: BACKGROUND
  Plasmodium falciparum merozoite surface protein 3 is a malaria vaccine candidate that was identified, characterised, and developed based on a unique immuno-clinical approach. The vaccine construct was derived from regions fully conserved among various strains and containing B cell epitopes targeted by human antibodies (from malaria-immune adults) that are able to mediate a monocyte-dependent parasite killing effect. The corresponding long synthetic peptide was administered to 36 volunteers, with either alum or Montanide ISA720 as adjuvant.
  
  
  RESULTS
  Both formulations induced cellular and humoral immune responses. With alum, the responses lasted up to 12 mo. The vaccine-induced antibodies were predominantly of cytophilic classes, i.e., able to cooperate with effector cells. In vitro, the antibodies induced an inhibition of the P. falciparum erythrocytic growth in a monocyte-dependent manner, which was in most instances as high as or greater than that induced by natural antibodies from immune African adults. In vivo transfer of the volunteers' sera into P. falciparum-infected humanized SCID mice profoundly reduced or abrogated parasitaemia. These inhibitory effects were related to the antibody reactivity with the parasite native protein, which was seen in 60% of the volunteers, and remained in samples taken 12 mo postimmunisation.
  
  
  CONCLUSIONS
  This is the first malaria vaccine clinical trial to clearly demonstrate antiparasitic activity by vaccine-induced antibodies by both in vitro and in vivo methods. The results, showing the induction of long-lasting antibodies directed to a fully conserved polypeptide, also challenge current concepts about malaria vaccines, such as unavoidable polymorphism, low antigenicity, and poor induction of immune memory.
authors.affiliation: Biomedical Parasitology Unit, Pasteur Institute, Paris, France. druilhe@pasteur.fr
authors.forename: Pierre
authors.initials: P
authors.lastname: Druilhe
authors.forename: François
authors.initials: F
authors.lastname: Spertini
authors.forename: Daw
authors.initials: D
authors.lastname: Soesoe
authors.forename: Giampietro
authors.initials: G
authors.lastname: Corradin
authors.forename: Pedro
authors.initials: P
authors.lastname: Mejia
authors.forename: Subhash
authors.initials: S
authors.lastname: Singh
authors.forename: Regine
authors.initials: R
authors.lastname: Audran
authors.forename: Ahmed
authors.initials: A
authors.lastname: Bouzidi
authors.forename: Claude
authors.initials: C
authors.lastname: Oeuvray
authors.forename: Christian
authors.initials: C
authors.lastname: Roussilhon
mesh_terms: D000276:Adjuvants, Immunologic / Q000008:administration & dosage; D000534:Alum Compounds / Q000008:administration & dosage; D000818:Animals; D000917:Antibody Formation; D001402:B-Lymphocytes / Q000276:immunology; D049109:Cell Proliferation; D006801:Humans; D007156:Immunologic Memory; D017780:Malaria Vaccines / Q000276:immunology*; D016778:Malaria, Falciparum / Q000276:immunology / Q000517:prevention & control*; D008353:Mannitol / Q000008:administration & dosage / Q000031:analogs & derivatives; D009829:Oleic Acids / Q000008:administration & dosage; D010963:Plasmodium falciparum / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology
chemical_list: D000276:Adjuvants, Immunologic; D000534:Alum Compounds; D017780:Malaria Vaccines; D009829:Oleic Acids; C001681:mannide monooleate; C041524:aluminum sulfate; D008353:Mannitol