title: Human immune recognition of recombinant proteins representing discrete domains of the Plasmodium falciparum gamete surface protein, Pfs230.
abstract: The 230 kD gametocyte/gamete-specific surface protein of Plasmodium falciparum, Pfs230, is a target of antibodies which inhibit the development of the parasite inside the mosquito vector. A transmission blocking vaccine based on Pfs230 may be a powerful tool for malaria control. As a first step, Pfs230 has been expressed in E. coli as a series of recombinant proteins, fused to maltose binding protein. We have used the fusion proteins to assess cellular and humoral immune responses to Pfs230 in malaria-immune adult Gambian blood donors; responses to the fusion proteins have been compared with responses to native Pfs230. The tetrapeptide repeat region of the molecule appears to be immunodominant for both antibody-producing cells and peripheral blood T cells. We postulate that this may represent a mechanism for immune evasion since the N-terminal repeat region of the molecule is cleaved from the mature protein and shed into the plasma. Responses to fusion proteins representing the seven-cysteine motifs were correlated within individual donors, suggesting that cross-reactive epitopes occur within the motifs. Antibody responses to recombinant proteins were poorly correlated with responses to native Pfs230 suggesting that dominant epitopes of the native protein are not adequately represented in the recombinant proteins. Although prokaryotic expression products may be suitable for induction of cellular immune responses to Pfs230, alternative expression systems may be needed for creation of appropriate B cell epitopes.
authors.affiliation: Institute of Cell, Animal and Population Biology, University of Edinburgh, UK.
authors.forename: E M
authors.initials: EM
authors.lastname: Riley
authors.forename: K C
authors.initials: KC
authors.lastname: Williamson
authors.forename: B M
authors.initials: BM
authors.lastname: Greenwood
authors.forename: D C
authors.initials: DC
authors.lastname: Kaslow
mesh_terms: D018528:ATP-Binding Cassette Transporters; D000293:Adolescent; D000328:Adult; D000818:Animals; D000913:Antibodies, Protozoan / Q000097:blood; D000953:Antigens, Protozoan / Q000276:immunology*; D001426:Bacterial Proteins / Q000276:immunology; D002352:Carrier Proteins / Q000276:immunology; D016022:Case-Control Studies; D004926:Escherichia coli / Q000276:immunology; D029968:Escherichia coli Proteins; D006801:Humans; D016056:Immunodominant Epitopes; D007371:Interferon-gamma / Q000097:blood; D008213:Lymphocyte Activation; D058619:Maltose-Binding Proteins; D008875:Middle Aged; D009004:Monosaccharide Transport Proteins; D010963:Plasmodium falciparum / Q000276:immunology*; D015800:Protozoan Proteins / Q000096:biosynthesis / Q000276:immunology*; D011994:Recombinant Proteins / Q000096:biosynthesis / Q000276:immunology*
chemical_list: D018528:ATP-Binding Cassette Transporters; D000913:Antibodies, Protozoan; D000953:Antigens, Protozoan; D001426:Bacterial Proteins; D002352:Carrier Proteins; D029968:Escherichia coli Proteins; D016056:Immunodominant Epitopes; D058619:Maltose-Binding Proteins; D009004:Monosaccharide Transport Proteins; D015800:Protozoan Proteins; D011994:Recombinant Proteins; C461599:maltose transport system, E coli; D007371:Interferon-gamma