Plasmodium falciparum: relevance of human antibodies for blocking transmission of the parasite from man to mosquito

Contains fulltext : mmubn000001_233317872.pdf (publisher's version ) (Open Access)Promotores : J. Meuwissen, R. Sauerwein en W. Eling127 p

Anti-NANP antibody and treatment efficacy in patients with acute uncomplicated falciparum malaria attacks.

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Anti-Pfs25 monoclonal antibody 32F81 blocks transmission from Plasmodium falciparum gametocyte carriers in Cameroon.

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Plasmodium falciparum: Membrane feeding assays and competition ELISAs for the measurement of transmission reduction in sera from Cameroon.

Item does not contain fulltextEpidemiological studies on the infectivity of Plasmodium falciparum gametocyte carriers to mosquitoes are important to estimate the human reservoir in malaria endemic areas and to evaluate the impact of conatrol measures aiming at reduction of malaria transmission. Muirhead Thomson (1957) investigated infectivity through direct feeding of batches of Anopheles gambiae on human subjects. Recent field studies used a similar approach (Gamage-Mendis et al. 1991; Githeka et al. 1992), but for ethical and practical reasons preference is often given to membrane feeding with blood from gametocyte carriers

Plasmodium falciparum: production and characterization of rat monoclonal antibodies specific for the sexual-stage Pfs48/45 antigen.

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Recombinant human antibodies specific for the Pfs48/45 protein of the malaria parasite Plasmodium falciparum.

Contains fulltext : 216407.pdf (Publisher’s version ) (Open Access)We report the first construction of two combinatorial human phage display libraries derived from malaria-immune patients. Specific single-chain Fv fragments (scFv) against Pfs48/45, a gamete surface protein of the sexual stages of Plasmodium falciparum, were selected and analyzed extensively. The selected scFv reacted with the surface of extracellular sexual forms of the parasite and showed Pfs48/45 reactivity on immunoblot. The scFv inhibit binding of human malaria sera to native Pfs48/45 from gametocytes. Moreover, the scFv bind to target epitopes of Pfs48/45 exposed in natural infections. Sequence analysis of eight scFv clones specific for epitope III of Pfs48/45 revealed that these clones could be divided into one V(H) family-derived germ-line gene (V(H)1) and two V(L) family segments (V(L)2 and V(K)I)

Human recombinant anti-La (SS-B) autoantibodies demonstrate the accumulation of phosphoserine-366-containing la isoforms in nucleoplasmic speckles.

Using the recombinant La (SS-B) protein or a phosphorylated peptide derived thereof 27 La-specific human recombinant autoantibodies were selected from anti-La-positive systemic lupus erythematosus and systemic sclerosis patient-derived combinatorial phage display antibody libraries. Binding of these anti-La antibodies to various isoforms of the La protein present in normal and apoptotic cell extracts was analysed by Western blotting. Twenty-four of the selected antibodies recognize most, if not all isoforms of La, whereas three are exclusively reactive with the protein phosphorylated at serine-366. Sequence analysis of the selected antibodies showed a restricted spectrum of diversity in their VH germline gene usage. Remarkably, the recombinant antibodies recognizing exclusively the phosphoserine-366-containing isoform of La displayed a spleckled nucleoplasmic staining pattern in immunofluorescence analysis of HeLa and HEp-2 cells. This pattern differed markedly from those obtained with anti-La antibodies recognizing all isoforms of the La protein. Colocalization experiments with marker antibodies for spliceosomal UsnRNPs and RNA polymerase III subunits revealed that the anti-phosphorylated La antibodies stain the same nucleoplasmic speckles as anti-UsnRNP antibodies. In contrast to anti-UsnRNP antibodies the anti-phosphorylated La antibodies did not stain the Cajal bodies. In addition, no colocalization of phosphorylated La with RNA polymerase III was observed. Potential functional implications of the accumulation of phosphorylated La in nucleoplasmic speckles are discussed

Isolation of a monoclonal antibody from a malaria patient-derived phage display library recognising the Block 2 region of Plasmodium falciparum merozoite surface protein-1.

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