title: Antibody responses to a novel Plasmodium falciparum merozoite surface protein vaccine correlate with protection against experimental malaria infection in Aotus monkeys.
abstract: The Block 2 region of the merozoite surface protein-1 (MSP-1) of Plasmodium falciparum has been identified as a target of protective immunity by a combination of seroepidemiology and parasite population genetics. Immunogenicity studies in small animals and Aotus monkeys were used to determine the efficacy of recombinant antigens derived from this region of MSP-1 as a potential vaccine antigen. Aotus lemurinus griseimembra monkeys were immunized three times with a recombinant antigen derived from the Block 2 region of MSP-1 of the monkey-adapted challenge strain, FVO of Plasmodium falciparum, using an adjuvant suitable for use in humans. Immunofluorescent antibody assays (IFA) against erythrocytes infected with P. falciparum using sera from the immunized monkeys showed that the MSP-1 Block 2 antigen induced significant antibody responses to whole malaria parasites. MSP-1 Block 2 antigen-specific enzyme-linked immunosorbent assays (ELISA) showed no significant differences in antibody titers between immunized animals. Immunized animals were challenged with the virulent P. falciparum FVO isolate and monitored for 21 days. Two out of four immunized animals were able to control their parasitaemia during the follow-up period, whereas two out of two controls developed fulminating parasitemia. Parasite-specific serum antibody titers measured by IFA were four-fold higher in protected animals than in unprotected animals. In addition, peptide-based epitope mapping of serum antibodies from immunized Aotus showed distinct differences in epitope specificities between protected and unprotected animals.
authors.affiliation: Institute of Immunology and Infection Research, Center for Immunity, Infection and Evolution, Ashworth Laboratories, University of Edinburgh, Edinburgh, United Kingdom.
authors.forename: David R
authors.initials: DR
authors.lastname: Cavanagh
authors.affiliation: Biomedical Primate Research Center, Department of Parasitology, Rijswijk, The Netherlands.
authors.forename: Clemens H M
authors.initials: CH
authors.lastname: Kocken
authors.affiliation: Institute of Immunology and Infection Research, Center for Immunity, Infection and Evolution, Ashworth Laboratories, University of Edinburgh, Edinburgh, United Kingdom.
authors.forename: John H
authors.initials: JH
authors.lastname: White
authors.affiliation: Institute of Immunology and Infection Research, Center for Immunity, Infection and Evolution, Ashworth Laboratories, University of Edinburgh, Edinburgh, United Kingdom.
authors.forename: Graeme J M
authors.initials: GJ
authors.lastname: Cowan
authors.affiliation: Scottish National Blood Transfusion Service, Cell Therapy Group, University of Edinburgh, Edinburgh, United Kingdom.
authors.forename: Kay
authors.initials: K
authors.lastname: Samuel
authors.affiliation: Biomedical Primate Research Center, Department of Parasitology, Rijswijk, The Netherlands.
authors.forename: Martin A
authors.initials: MA
authors.lastname: Dubbeld
authors.affiliation: Biomedical Primate Research Center, Department of Parasitology, Rijswijk, The Netherlands.
authors.forename: Annemarie
authors.initials: A
authors.lastname: Voorberg-van der Wel
authors.affiliation: Biomedical Primate Research Center, Department of Parasitology, Rijswijk, The Netherlands.
authors.forename: Alan W
authors.initials: AW
authors.lastname: Thomas
authors.affiliation: Institute of Immunology and Infection Research, Center for Immunity, Infection and Evolution, Ashworth Laboratories, University of Edinburgh, Edinburgh, United Kingdom.
authors.forename: Jana S
authors.initials: JS
authors.lastname: McBride
authors.affiliation: Institute of Immunology and Infection Research, Center for Immunity, Infection and Evolution, Ashworth Laboratories, University of Edinburgh, Edinburgh, United Kingdom.
authors.forename: David E
authors.initials: DE
authors.lastname: Arnot
mesh_terms: D000276:Adjuvants, Immunologic; D000595:Amino Acid Sequence; D000818:Animals; D000917:Antibody Formation / Q000276:immunology*; D000918:Antibody Specificity / Q000276:immunology; D000953:Antigens, Protozoan / Q000276:immunology; D018604:Epitope Mapping; D000939:Epitopes / Q000737:chemistry / Q000276:immunology; D000882:Haplorhini / Q000097:blood / Q000276:immunology* / Q000469:parasitology; D006801:Humans; D007114:Immunization; D017780:Malaria Vaccines / Q000276:immunology*; D016778:Malaria, Falciparum / Q000097:blood / Q000276:immunology* / Q000469:parasitology / Q000517:prevention & control*; D020066:Merozoite Surface Protein 1 / Q000276:immunology*; D008969:Molecular Sequence Data; D018512:Parasitemia / Q000276:immunology / Q000469:parasitology; D010963:Plasmodium falciparum / Q000276:immunology*; D011994:Recombinant Proteins / Q000276:immunology
chemical_list: D000276:Adjuvants, Immunologic; D000953:Antigens, Protozoan; D000939:Epitopes; D017780:Malaria Vaccines; D020066:Merozoite Surface Protein 1; D011994:Recombinant Proteins