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

Erythrocytes infected with malaria parasites often contain membranous vesicles that are presumed to facilitate macromolecule traffic between the parasite and erythrocyte membranes. One such vesicle network, called Maurer's clefts, is expressed in Plasmodium falciparum-infected erythrocytes and contains a 50-kD polypeptide. Using a monoclonal antibody reactive with this polypeptide, we show that hepatic stages of P. falciparum express an epitope common to this blood-stage antigen. In addition, this epitope is cross-reactive with antigens expressed by primate leukocytes and platelets. Such epitopes may induce autoantibodies commonly seen in patients with malaria.
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PMID:Cross-reactive epitope among proteins in Plasmodium falciparum Maurer's clefts and primate leukocytes and platelets. 868 88

Malaria, especially that caused by Plasmodium falciparum, is the most important parasitic disease of man. The complexity of the life cycle, the transmission dynamics in different endemic settings, and the spread of resistance to various drugs by the parasite and to insecticides by the vector render control strategies very difficult. An effective vaccine against malaria would represent a major strengthening of control. Research efforts to identify and select antigens for vaccine development have been substantial, particularly in the past 20 years. Various molecules from the pre-erythrocytic, asexual blood and sexual stages have been described and tested in experimental systems, and some may become interesting vaccine candidates. A crucial step was taken with the development of SPf66, a synthetic polypeptide based on pre-erythrocytic and asexual blood-stage proteins of Plasmodium falciparum. The concept of the SPf66 vaccine is not the prevention of clinical malaria but reduction of morbidity, and it is thus suitable for endemic areas, particularly Africa. The clinical phase III trials so far undertaken in Latin America and in Africa have clearly documented the safety, immunogenicity and partial efficacy of SPf66 against clinical malaria. The efficacy estimates of all trials are below those we generally demand from vaccines and when we aim to induce sterile immunity. Therefore, a large number of issues at the field and laboratory levels, such as ways of optimizing efficacy (doses, timing, age of vaccination), and understanding the mechanisms of action and effectiveness, need to be investigated before one can consider the public health use of SPf66 as a component of an integrated malaria control programme. The substantial tasks ahead involve (1) improving the vaccine which we have and (2) devising and testing new vaccines which may prove more efficacious. Malaria vaccines are now a reality, and the achievements of SPf66 to date, the ongoing research efforts with other vaccine candidates, and the potential of DNA vaccines make it possible to predict that widespread use of an efficacious vaccine no longer represents an unrealistic target.
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PMID:The development of malaria vaccines: SPf66--what next? 876 32

The carboxy-terminus of the major merozoite surface protein of Plasmodium has been shown to be the target of protective immunity in a number of non-vivax malaria parasite species. In an effort to develop a protective vaccine for Plasmodium vivax, the most prevalent form of human malaria, we expressed in Saccharomyces cerevisiae the 19-kDa a carboxy-terminus of Pv200 as a His6-tagged, secreted polypeptide. Five of seven H-2 congenic mouse strains elicited antibodies that recognized yeast produced PV200(19) by ELISA. The vaccine appears to be immunogenic and widely recognized, and to contain one or more helper T cell epitopes that may allow boosting with subsequent natural infections.
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PMID:Expression and immunogenicity of the C-terminus of a major blood-stage surface protein of Plasmodium vivax, Pv200(19), secreted from Saccharomyces cerevisiae. 883 90

During the course of chronic malaria infection antigenic variants of a parasite antigen are expressed and exposed on the surface of infected erythrocyte membranes. There also exists a number of apparently invariant single gene copy blood-stage antigens, exposed or non-exposed, which have been shown to afford immunity under experimental conditions. To determine why the host, presented with invariant 'protective' antigens, is unable to control infections effectively, immunity to a representative single gene copy antigen, the merozoite surface protein 1 (MSP1) was investigated in Plasmodium chabaudi chabaudi AS, a murine model of chronic malaria. Immunization with monoclonal antibody affinity purified native MSP1 resulted in enhanced control of parasitaemia on challenge, irrespective of the parasite inoculum size; challenge with a single parasite, however, suggested that expansion of resistant parasite subpopulations was not occurring. Challenge of mice immunized with recombinant fusion proteins encoding N- or C-terminal regions of the P.c. chabaudi AS MSP1 produced inconsistent effects, often parasitaemias were indistinguishable from controls despite significant anti-MSP1 antibody responses. The not unlikely contamination of MSP1 native preparations with erythrocyte (E) components was considered. Immunization with a mixture of the MSP1 C-terminus recombinant polypeptide and a Triton X-100 solubilized lysate of normal E resulted in enhanced control of parasitaemia, however, no effect was seen after administration of either component on its own. Co-immunization of E with the N-terminus polypeptide reversed the inhibition seen, on this occasion with this construct alone.
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PMID:A single gene copy merozoite surface antigen and immune evasion? 922 71

The erythrocyte binding antigen EBA-175 is a 175-kDa Plasmodium falciparum protein which mediates merozoite invasion of erythrocytes in a sialic acid-dependent manner. The purpose of this study was to produce recombinant EBA-175 polypeptide domains which have previously been identified as being involved in the interaction of EBA-175 with erythrocytes and to determine whether these polypeptides are recognized by malaria-specific antibodies. The eba-175 gene was cloned by PCR from genomic DNA isolated from the 3D7 strain of P. falciparum. The predicted protein sequence was highly conserved with that predicted from the published eba-175 gene sequences from the Camp and FCR-3 strains of P. falciparum and contained the F segment divergent region. Purified recombinant EBA-175 polypeptide fragments, expressed as glutathione S-transferase fusion proteins in insect cells by using the baculovirus system, were recognized by antibodies present in serum from a drug-cured, malaria-immune Aotus nancymai monkey. The fusion proteins were also recognized by antibodies present in sera from individuals residing in areas where malaria is endemic. In both cases the antibodies specifically recognized the EBA-175 polypeptide portion of the fusion proteins. Antibodies raised in rabbits immunized with the recombinant fusion proteins recognized parasite proteins present in schizont-infected erythrocytes. Our results suggest that these regions of the EBA-175 protein are targets for the immune response against malaria and support their further study as possible vaccine components.
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PMID:Baculovirus-mediated expression of Plasmodium falciparum erythrocyte binding antigen 175 polypeptides and their recognition by human antibodies. 928 29

An endoplasmic reticulum-located, calcium-binding protein, with an apparent molecular weight (Mr) of approximately 40,000 (PfERC), has been identified in the asexual stages of the malaria parasite, Plasmodium falciparum. This protein appears to be equivalent to a previously described gametocyte protein, Pfs40, which was reported to be expressed on the gametocyte surface (Rawlings DJ, Kaslow DC. J Biol Chem 1992;267:3976-3982). Sequencing of the 3' end of the gene revealed the omission of a single base in the 3' region of the published sequence. The corrected gene sequence encodes a C-terminal IDEL motif, which indicates residency of the 40 kDa protein within the endoplasmic reticulum. The predicted C-terminal region also appears to contain a sixth EF-hand calcium-binding domain, which suggests that PfERC is related to previously reported ER-localized calcium-binding proteins, namely reticulocalbin and ERC-55 (Ozawa M. J. Biochem. 1995;117:1113-1119; Weis K, Griffiths G, Lamond AI. J. Biol. Chem. 1994;269:19142-19150). The presence of the 40 kDa calcium-binding protein in malaria parasites was confirmed using 45Ca2+-blotting and partial protein sequencing of the corresponding Coomassie blue-stained polypeptide. Confocal immunofluorescence microscopy of asexual stage parasites was used to show that PfERC co-localizes with the known ER-located protein, Pfgrp. Analysis of immunoblots of tightly synchronized parasites showed that expression of PfERC increases with increasing maturity of the parasite. We propose that PfERC is a member of the reticulocalbin family of calcium-binding proteins and may play a role in protein trafficking in the malaria parasite.
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PMID:Identification of an endoplasmic reticulum-resident calcium-binding protein with multiple EF-hand motifs in asexual stages of Plasmodium falciparum. 936 72

Phenol oxidase exists in insect hemolymph as a zymogen, pro-phenol oxidase (pro-PO), which is activated by specific proteolysis in response to infection or wounding. Phenol oxidase catalyses the synthesis of quinones that polymerize to form melanin deposits, which encapsulate parasites and help to seal wounds. Antibodies to pro-PO from Manduca sexta bound to 76, 72, and 71 kDa polypeptide bands from hemolymph of Anopheles gambiae larvae. This antiserum was used to screen a cDNA library from A. gambiae fourth-instar larvae. Full-length clones were isolated for two different pro-POs, designated A. gambiae proPO-p1 and proPO-p2, which are 67% identical in nucleotide sequence and 66% identical in deduced amino acid sequence. The A. gambiae pro-PO sequences are more similar to pro-PO from Drosophila melanogaster than to lepidopteran or crustacean pro-PO sequences in the GenBank database. Like the other arthropod pro-POs, the A. gambiae pro-PO sequences lack a signal peptide and have two conserved regions predicted to bind two copper atoms in the active site of the enzyme. The availability of these pro-PO cDNAs should be useful in examining the biochemical differences between A. gambiae strains that are refractory or susceptible to Plasmodium infection, and differ in their ability to encapsulate the parasites.
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PMID:Molecular cloning of cDNAs for two pro-phenol oxidase subunits from the malaria vector, Anopheles gambiae. 940 13

A cDNA clone for prophenoloxidase was isolated from the most important human malaria vector, Anopheles gambiae. The clone encoded a polypeptide of 79341 Da that contains the two copper binding domains common to all invertebrate prophenoloxidases and haemocyanins. Expression of the prophenoloxidase gene was detected throughout all life stages from egg to imago in two strains of A. gambiae; however, the strongest expression was observed in developing embryos in eggs. The prophenoloxidase gene was mapped to the inversion rich region of the right arm of chromosome-2 in region 13B.
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PMID:Molecular cloning and chromosomal localization of a prophenoloxidase cDNA from the malaria vector Anopheles gambiae. 945 28

Plasmodium vivax is a very common human malaria parasite but it is poorly characterized at the molecular level. Here, we describe the isolation and characterization of an antigen coding gene of P. vivax which contains Alu elements. This gene, called Pv-Alu, is expressed during the erythrocytic phase of the parasite. The encoded 200 amino acid long polypeptide is highly hydrophobic, contains transmembrane domains, and is rich in leucine (19.4%), serine (15.9%), proline (15.4%) and phenylalanine (15.4%). The 5'-untranslated region and part of the 3'-end coding region of Pv-Alu show significant homology to different Alu families. The presence of Alu elements in the coding region of a parasite antigen gene is significant from a functional and evolutionary viewpoint.
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PMID:Alu elements in a Plasmodium vivax antigen gene. 951 56

In 1994, 630 Gambian infants were immunized with three doses of the synthetic polypeptide malaria vaccine SPf66 or with a control vaccine. No significant protection against first or total attacks of malaria was observed among the children who received SPf66. However, the period of follow-up was short. Thus, 532 children were followed for a second malaria transmission season during which 291 episodes of malaria were detected. Protective efficacies of SPf66 against first attacks of malaria and against all attacks of malaria were 8% [95% CI-20%, 30%] and 2% [95% CI-26% 24%] respectively. SPf66 did not provide any significant degree of protection to Gambian infants during a second year of follow-up.
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PMID:An efficacy trial of the malaria vaccine SPf66 in Gambian infants--second year of follow-up. 960 10


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