title: A multi-stage malaria vaccine candidate targeting both transmission and asexual parasite life-cycle stages.
abstract: Effective control and eventual eradication of malaria drives the imperative need for clinical development of a malaria vaccine. Asexual parasite forms are responsible for clinical disease and death while apathogenic gametocytes are responsible for transmission from man to mosquito. Vaccines that combine antigens from both stages may provide direct protection and indirect benefit by reducing the force of infection. We constructed a chimeric antigen composed of a fragment of the Plasmodium falciparum (Pf) glutamate-rich protein fused in frame to a correctly folded fragment of Pfs48/45. The chimera was produced in Lactococcus lactis and induced robust antibody responses in rodents to the individual components. Specific antibodies showed strong transmission blocking activity against multiple Pf-strains in the standard membrane feeding assay and functional activity against asexual stages in the antibody dependent cellular inhibition assay. The combined data provide a strong rationale for entering the next phase of clinical grade production and testing.
authors.affiliation: Department of Clinical Biochemistry, Immunology and Genetics, Statens Serum Institut, Copenhagen, Denmark; Centre for Medical Parasitology at Department of International Health, Immunology and Microbiology, University of Copenhagen and Department of Infectious Diseases, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark. Electronic address: mth@ssi.dk.
authors.forename: Michael
authors.initials: M
authors.lastname: Theisen
authors.affiliation: Department of Medical Microbiology, Radboud University Nijmegen Medical Center, Nijmegen, the Netherlands.
authors.forename: Will
authors.initials: W
authors.lastname: Roeffen
authors.affiliation: Department of Clinical Biochemistry, Immunology and Genetics, Statens Serum Institut, Copenhagen, Denmark; Centre for Medical Parasitology at Department of International Health, Immunology and Microbiology, University of Copenhagen and Department of Infectious Diseases, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark.
authors.forename: Susheel K
authors.initials: SK
authors.lastname: Singh
authors.affiliation: Centre for Medical Parasitology at Department of International Health, Immunology and Microbiology, University of Copenhagen and Department of Infectious Diseases, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark.
authors.forename: Gorm
authors.initials: G
authors.lastname: Andersen
authors.affiliation: Noguchi Memorial Institute for Medical Research, University of Ghana, Ghana.
authors.forename: Linda
authors.initials: L
authors.lastname: Amoah
authors.affiliation: Department of Medical Microbiology, Radboud University Nijmegen Medical Center, Nijmegen, the Netherlands.
authors.forename: Marga
authors.initials: M
authors.lastname: van de Vegte-Bolmer
authors.affiliation: Department of Medical Microbiology, Radboud University Nijmegen Medical Center, Nijmegen, the Netherlands.
authors.forename: Theo
authors.initials: T
authors.lastname: Arens
authors.affiliation: Department of Clinical Biochemistry, Immunology and Genetics, Statens Serum Institut, Copenhagen, Denmark; Centre for Medical Parasitology at Department of International Health, Immunology and Microbiology, University of Copenhagen and Department of Infectious Diseases, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark.
authors.forename: Régis Wendpayangde
authors.initials: RW
authors.lastname: Tiendrebeogo
authors.affiliation: Department of Immunology & Infection, London School of Hygiene & Tropical Medicine, London, United Kingdom.
authors.forename: Sophie
authors.initials: S
authors.lastname: Jones
authors.affiliation: Department of Medical Microbiology, Radboud University Nijmegen Medical Center, Nijmegen, the Netherlands; Department of Immunology & Infection, London School of Hygiene & Tropical Medicine, London, United Kingdom.
authors.forename: Teun
authors.initials: T
authors.lastname: Bousema
authors.affiliation: Department of Clinical Biochemistry, Immunology and Genetics, Statens Serum Institut, Copenhagen, Denmark; Centre for Medical Parasitology at Department of International Health, Immunology and Microbiology, University of Copenhagen and Department of Infectious Diseases, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark.
authors.forename: Bright
authors.initials: B
authors.lastname: Adu
authors.affiliation: Blood Bank KI 2034, Rigshopitalet, Department of Clinical Immunology, Capital Region, Copenhagen, Denmark.
authors.forename: Morten H
authors.initials: MH
authors.lastname: Dziegiel
authors.affiliation: Department of Clinical Biochemistry, Immunology and Genetics, Statens Serum Institut, Copenhagen, Denmark.
authors.forename: Michael
authors.initials: M
authors.lastname: Christiansen
authors.affiliation: Department of Medical Microbiology, Radboud University Nijmegen Medical Center, Nijmegen, the Netherlands.
authors.forename: Robert
authors.initials: R
authors.lastname: Sauerwein
mesh_terms: D000818:Animals; D000852:Anopheles; D000913:Antibodies, Protozoan / Q000097:blood; D000917:Antibody Formation; D007106:Immune Sera / Q000276:immunology; D007074:Immunoglobulin G / Q000097:blood; D017780:Malaria Vaccines / Q000276:immunology*; D016778:Malaria, Falciparum / Q000517:prevention & control*; D008562:Membrane Glycoproteins / Q000276:immunology*; D010963:Plasmodium falciparum; D015800:Protozoan Proteins / Q000276:immunology*; D017208:Rats, Wistar; D011994:Recombinant Proteins / Q000276:immunology; D022223:Vaccines, Subunit / Q000276:immunology
chemical_list: D000913:Antibodies, Protozoan; D007106:Immune Sera; D007074:Immunoglobulin G; D017780:Malaria Vaccines; D008562:Membrane Glycoproteins; D015800:Protozoan Proteins; D011994:Recombinant Proteins; D022223:Vaccines, Subunit; C084847:pfs48-45 protein, Plasmodium falciparum; C072492:glutamate-rich protein, Plasmodium
keywords: ADCI; GLURP; Pfs48/45; Plasmodium falciparum; SMFA; transmission blocking