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Query: UMLS:C0024530 (malaria)
 44,886 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We describe an immunoadhesin molecule containing intercellular adhesion molecule 1 (ICAM-1) molecularly fused to hinge and CH2 and CH3 domains of the human immunoglobulin G1 H chain that binds Plasmodium falciparum-infected erythrocytes. This receptor-based immunoadhesin is an effective and specific inhibitor of P. falciparum-infected erythrocyte adhesion to ICAM-1-bearing surfaces, but does not inhibit leukocyte function antigen 1 (LFA-1) interaction with ICAM-1. Furthermore, the immunoadhesin promotes phagocytosis and destruction of parasitized erythrocytes by human monocytes. Each of these modes of action has potential for the therapy of malaria.
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PMID:Soluble intercellular adhesion molecule 1-immunoglobulin G1 immunoadhesin mediates phagocytosis of malaria-infected erythrocytes. 138 88

A Plasmodium falciparum genomic DNA library was established in the expression vector lambda gt11, cloned in Escherichia coli. The library was screened with human hyperimmune sera by in situ hybridization. Twenty clones expressing P. falciparum sequences as polypeptides fused to beta-galactosidase were identified. One, CD3A/9025/60, reacted with all immune sera and expressed polypeptides that were larger than beta-galactosidase as well as reacting with antibodies to beta-galactosidase and to P. falciparum. When the fusion proteins were used as target antigens to diagnose malaria antibodies, a result was obtained which correlated well with indirect fluorescence assay.
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PMID:Molecular cloning of Plasmodium falciparum blood stage antigens and application of the recombinant proteins in serodiagnosis. 148 92

An expression system to allow targeting of heterologous proteins to the cell surface of Staphylococcus xylosus, a coagulase-negative gram-positive bacterium, is described. The expression of recombinant gene fragments, fused between gene fragments encoding the signal peptide and the cell surface-binding regions of staphylococcal protein A, targets the resulting fusion proteins to the outer bacterial cell surface via the membrane-anchoring region and the highly charged cell wall-spanning region of staphylococcal protein A. The expression system was used to secrete fusion proteins containing sequences from a malaria blood-stage antigen and a streptococcal albumin-binding receptor to the cell surface of S. xylosus. Analysis of the recombinant cells by immunogold staining and immunofluorescence revealed that both the receptor and the malaria peptide were properly processed and exposed on the surface of the host cells. However, only approximately 40 to 50% of the recombinant cells were strongly stained with antiserum reactive with the albumin-binding receptor, while approximately 10 to 15% of the cells were stained with antiserum reactive with the malaria peptide. The incomplete staining of some of the cells suggests steric effects that make the recombinant fusion proteins inaccessible to the reactive antibodies because of variable cell wall structures. However, the results demonstrate for the first time that recombinant techniques can be used to express heterologous receptors and immunogens on the surface of gram-positive cells.
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PMID:Expression of recombinant proteins on the surface of the coagulase-negative bacterium Staphylococcus xylosus. 162 18

Erythrocytes from Aotus and Saimiri monkeys parasitized by Plasmodium vivax show dramatic changes starting during the early stages of parasite development. Invaginations of the erythrocyte membrane, caveolae, are found during all parasite development stages. Up to six vesicles can be fused with one caveola, forming a caveola-vesicle complex. As the parasite grows, large accumulations of these vesicles can be seen within the erythrocyte cytoplasm. In addition to these caveolae-vesicle complexes, knob-like structures appear on the erythrocyte surface that are similar to those seen on the host-cell surface of P. falciparum-infected red cells. Extensive membrane-bound clefts spread throughout the erythrocytic cytoplasm, sometimes forming stacks or large whorls. The density of the red cell cytoplasm begins to decrease at an early stage of parasite development. All of these changes may be responsible for an increased fragility of the P. vivax-infected red cell from Aotus or Saimiri monkeys. Moreover, the large amount of parasite material that is released during rupture of the red cell may account for the high fever paroxysms that are characteristic of P. vivax malaria infection.
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PMID:Ultrastructure of erythrocytes from Aotus trivirgatus and Saimiri sciureus monkeys infected by Plasmodium vivax. 189 48

The Escherichia coli OmpA protein can serve as a carrier for the expression of foreign antigens on the surface of gram-negative bacteria. Employing OmpA vectors, immunogenic moieties of the Plasmodium falciparum blood stage antigens SERP and HRPII have been expressed in the attenuated Salmonella typhimurium SR-11 strain. Upon induction, the malaria specific sequences of 189 (HRPII) and 451 (SERP) amino acids, fused into the OmpA protein, have been expressed. By indirect immunofluorescence studies, live bacteria expressing the fusion proteins react anti-SERP and anti-HRPII sera, respectively, indicating that the hybrid OmpA proteins become integrated into the bacterial outer membrane and expose the malarial antigens at the exterior surface. Mice that were immunized orally with S. typhimurium cells expressing HRPII and SERP on their surface show a humoral immune response as determined by the anti-SERP and anti-HRPII IgG and IgM titres. From these experiments it can be concluded that the OmpA surface expression system in combination with established Salmonella vaccine strains can be used to efficiently deliver large antigens to the mucosal immune system.
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PMID:Surface expression of malarial antigens in Salmonella typhimurium: induction of serum antibody response upon oral vaccination of mice. 195 99

A method for purification of a recombinant Plasmodium falciparum protein produced in E. coli and its use in an enzyme-linked immunosorbent assay (ELISA) is described. The cloned gene fragment encodes GLURP,489-1271 the carboxy-terminal 783 amino acid residue portion of a 1271 amino acid residue P. falciparum glutamate rich protein (GLURP), with a molecular weight of 220 kilodalton. The protein is associated with all parasite stages in the human host. Examination of sera from 105 adult Liberians living in a malaria endemic area revealed anti-GLURP IgG antibodies in 98% of the sera. The recombinant GLURP489-1271 was expressed as a chimeric protein, fused with E. coli beta-galactosidase. However, antibodies in sera were directed only against the malaria part of the fusion protein and not against beta-galactosidase. Antigen from in vitro P. falciparum cultures of isolates from Tanzania (F32), Papua New Guinea (MAD20) and Honduras (HB3) completely absorbed specific antibodies, indicating the presence of conserved epitopes produced by all isolates of P. falciparum. Recombinant GLURP489-1271 ELISA is sensitive and rapid, and therefore well-suited for sero-epidemiological studies, and for control of the immunogenicity of a possible future P. falciparum vaccine utilizing epitopes from GLURP.
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PMID:Recombinant Plasmodium falciparum glutamate rich protein; purification and use in enzyme-linked immunosorbent assay. 203 52

We have expressed defined regions of the serine-repeat antigen (SERA) of the Honduras-1 strain of Plasmodium falciparum in the yeast Saccharomyces cerevisiae. Amino-terminal domains of the natural SERA protein have been shown previously to be targets for parasite-inhibitory murine monoclonal antibodies. Two recombinant SERA antigens were selected for purification and immunological analysis. The first (SERA 1), corresponding to amino acids 24-285 of the natural SERA precursor, was expressed by the ubiquitin fusion method. This allowed for in vivo cleavage by endogenous yeast ubiquitin hydrolase, and subsequent isolation of the mature polypeptide. The second, larger protein (SERA N), encompassing amino acids 24-506, was expressed at only low levels using this system, but could be isolated in high yields when fused to human gamma-interferon (gamma-IFN). Each purified protein was used to immunize mice with either Freund's adjuvant or a muramyl tripeptide adjuvant that has been used in humans. Sera from immunized mice were shown to be capable of in vitro inhibition of invasion of erythrocytes by the Honduras-1 strain of P. falciparum. The results suggest that a recombinant SERA antigen may be an effective component of a candidate malaria vaccine.
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PMID:Immunogenicity of recombinant Plasmodium falciparum SERA proteins in rodents. 205 35

We have expressed two cDNA sequences encoding 121 and 230 amino acids of the C-terminus of the Schistosoma mansoni Hsp 70 in Escherichia coli. The products were synthesized as polypeptides fused to the RNA polymerase of bacteriophage MS2, and their reactivities were tested in ELISAs, using sera from human and murine infections. Anti-Hsp70 antibodies were detected in a significant number of individuals suffering from chronic schistosomiasis mansoni, but not in patients with known recent infections. This, together with the finding that antibodies directed at S. mansoni-specific Hsp70 determinants during the course of infection of experimental mice were not detectable until 5-6 weeks post-infection, suggests that the protein may be a useful marker for distinguishing late and early infections. The diagnostic specificity of Hsp70 was evaluated with sera from humans infected with different schistosome species and other parasitic diseases. While some subjects infected with S. haematobium produced antibodies which recognized the S. mansoni Hsp70, no such antibodies were generated in S. japonicum infected individuals. However, cross-reactive antibodies were elicited in donors with other parasitic diseases such as filariasis and malaria. The absence of antibodies in early infection and the observed cross-reactivities led us to conclude that Hsp70 will be of limited value in the diagnosis of schistosomiasis.
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PMID:The humoral response to heat shock protein 70 in human and murine Schistosomiasis mansoni. 211 91

We describe a cDNA clone derived from mRNA of asexual blood-stages of the malaria parasite Plasmodium falciparum. This clone, designated Ag319, expresses a P.falciparum antigen fused to beta-galactosidase in Escherichia coli. Human antibodies from Papua New Guinea were affinity-purified by adsorption to extracts of Ag319 immobilized on CNBr-Sepharose. The antibodies reacted predominantly with P. falciparum polypeptides of Mr 220,000 and 160,000, and a number of ill-defined lower molecular weight species. Antibodies reacted in indirect immunofluorescence with all asexual blood-stages although the antigen appeared to be most abundance in the schizont. Surprizingly the antibodies also reacted with sporozoites. The amino acid sequence predicted from the complete nucleotide sequence of this clone is remarkable because 40% of the residues are Asn, and so the antigen has been termed the Asparagine-Rich Protein (ARP). Like other P. falciparum antigens, ARP contains tandemly repetitive sequences, based on the tetrapeptide Asn-Asn-Asn-Met and we have confirmed that these represent natural epitopes by reaction of the corresponding synthetic peptides with human antibodies. Surprisingly, ARP is also rich in Asn outside the tandem repeats.
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PMID:An asparagine-rich protein from blood stages of Plasmodium falciparum shares determinants with sporozoites. 242 Dec 57

Recent studies have identified and characterized a ring-infected erythrocyte surface antigen (RESA) of the human malaria parasite Plasmodium falciparum with a relative molecular mass (Mr) of approximately 155,000 (refs 1-7). RESA is localized in the micronemes of merozoites and also the membrane of red cells infected with ring-stage parasites. It is thought to be released through the apical pore from the rhoptry at the time of merozoite invasion. Because antibodies directed against this antigen strongly inhibit parasite growth in vitro, RESA may be useful in developing a vaccine against this parasite Here we describe an immunization trial using Aotus monkeys and Escherichia coli-derived fused polypeptides corresponding to various regions of the RESA molecule. Some monkeys in all test groups, but not in the control group, were protected against overwhelming infection. Strikingly, protection correlated with antibody responses to either of two different repetitive sequences in RESA.
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PMID:Immunization of Aotus monkeys with recombinant proteins of an erythrocyte surface antigen of Plasmodium falciparum. 242 87


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