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

To evaluate the ability of antibodies to Plasmodium falciparum ring-infected erythrocyte surface antigen (Pf155/RESA) epitopes to discriminate between individuals well protected or poorly protected against malaria, a receiver operating characteristic analysis was performed in two populations living in Madagascar and Malawi. The definition of protection was based on longitudinal measurements of clinical malarial attacks during the season of high malaria transmission in the Madagascar study, and on a cross-sectional measurement of parasitemia in the Malawi study. Antibodies to peptides reproducing the 4-mer, 8-mer, and 11-mer of the Pf155/RESA were tested for their reactivities using the Falcon assay screening test-enzyme-linked immunosorbent assay. Maximal detection of poorly protected individuals (specificity = 100%) corresponded to high cutoff antibody titers (range = 1.65-3.0 optical density [OD] units in the Madagascar study and 0.67-1.42 OD units in the Malawi study) and a sensitivity less than 50%. For a given sensitivity of 50%, specificity ranged from 55% to 62% in the Madagascar study, and from 67% to 94% in the Malawi study. The antibody cutoff titers corresponding to minimal misclassification rates ranged from 0.24 to 1.73 OD units in the Madagascar study and from 0.15 to 0.55 OD units in the Malawi study. For each antibody, the highest detectability value as measured by the area under the curve was obtained for anti-R11 in the Malawi study (0.838). In demonstrating such qualities, antibodies to Pf155/RESA epitopes could be used for screening poorly protected populations in which malaria control programs have to be implemented.
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PMID:Antibodies to a Plasmodium falciparum blood-stage antigen as a tool for predicting the protection levels of two malaria-exposed populations. 754 43

Previously, CD4+ T cell lines and clones were isolated after immunization of BALB/c and C57BL/6 mice with the Py1 peptide, a 21-mer synthetic peptide corresponding to a N-terminal segment of the circumsporozoite protein of Plasmodium yoelii. The clones were separated into the Th1 and Th2 subsets on the basis of lymphokine production. It was observed that immunization with the Py1 peptide induced preferentially Th1 cells in BALB/c and Th2 cells in C57BL/6 mice. These clones were then tested for their cytolytic ability in vitro. Some of the clones from BALB/c and C57BL/6 mice eliminated liver stage parasites from cultured hepatocytes in a MHC restricted manner. Nevertheless, none of these clones was able to lyse Py1 peptide-pulsed target cells. It was also found that two clones could protect BALB/c mice against a sporozoite challenge. These results provide evidence that CD4+ T cells, induced after priming with a defined peptide, could participate in the effector mechanisms against malaria liver stages.
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PMID:Effector functions of circumsporozoite peptide-primed CD4+ T cell clones against Plasmodium yoelii liver stages. 767 28

CD4+ T cell clones were derived from three volunteers who were protected against malaria after immunization with Plasmodium falciparum sporozoites. T cells specific for an epitope, Pf Th/Tc, contained in amino acids 326 to 345 of the circumsporozoite (CS) protein of P. falciparum (NF54) were derived from all three volunteers. DR1-, -4-, -7-, and -9-restricted T cell clones were found to recognize overlapping, but distinct, epitopes within a 20-mer peptide representing the amino acid 326 to 345 sequence. The Pf Th/Tc epitope contains part of the highly conserved region II as well as part of a polymorphic domain of the P. falciparum CS protein. All of the overlapping epitopes within peptide 326-345 contained at least three amino acids of the amino terminus of the conserved region II, in addition to a variable number of amino acids in the polymorphic region. The DR4-, -7-, and -9-restricted but not the DR1-restricted T cell clones recognized variant peptides representing this polymorphic region of the CS protein of P. falciparum isolates from Africa, Asia, and South America.
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PMID:CD4+ T cell clones obtained from Plasmodium falciparum sporozoite-immunized volunteers recognize polymorphic sequences of the circumsporozoite protein. 768 46

One approach towards the development of a vaccine against malaria is to immunize against the parasite sexual stages that mediate transmission of the parasite from man to mosquito. Antibodies against these stages, ingested with the blood meal, inhibit the parasite development in the mosquito vector, constituting "transmission blocking immunity." Most epitopes involved in transmission-blocking immunity depend on the tertiary conformational structure of surface antigens. However, one of the transmission-blocking monoclonal antibodies we have raised against Plasmodium vivax reacts with a linear epitope on both asexual stages and gametes. This monoclonal antibody (A12) is capable of totally blocking development of the parasite in the mosquito host when tested in membrane feeding assays with gametocytes from P. vivax-infected patients. Immune screening of a P. vivax lambda gt11 genomic expression library with A12 led to the isolation of a clone to which was mapped the six-amino acid epitope recognized by A12. Antisera raised in mice against a 12-mer synthetic peptide containing this epitope coupled to bovine serum albumin not only had high titers of antipeptide antibodies as measured by enzyme-linked immunosorbent assay, but in addition recognized the same 24- and 57-kD parasite components as A12 on Western blots and reacted with the parasite by immunofluorescence. When tested in membrane feeding assays, these antibodies have significant suppressive effects on parasite development in the mosquito.
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PMID:Transmission blocking immunity in Plasmodium vivax malaria: antibodies raised against a peptide block parasite development in the mosquito vector. 780 16

The effects of exogenously applied oligodeoxynucleotides on Plasmodium falciparum proliferation was investigated. A fluorescence-activated cell sorter assay was employed to measure parasitemia after administration of either phosphodiester or phosphorothioate oligodeoxynucleotides. We report sequence-independent antimalarial activity preferentially with phosphorothioate congeners with IC50 values in the 1-2 microM range. Phosphorothioate oligodeoxynucleotides which were antisense, sense or nonsense to Plasmodium mRNA, as well as homopolymers (30-mers containing all A or T bases) were equally effective inhibitors of parasitemia. The antimalarial activity was dependent upon oligomer length, concentration, and time of addition to the cultures but was independent of the parasite strain tested. Four P. falciparum strains, including a multi-drug-resistant strain (MDR-K), a drug-sensitive strain (FCR-3), a erythrocyte membrane sialic acid-independent strain (7G8) and a strain isolated from a cerebral malaria patient (CM-87) were equally susceptible to treatment with a phosphorothioate oligomer. Inhibition of red cell invasion is primarily responsible for the observed decrease in proliferation as determined by a study of parasite maturation in the presence of a 30-mer nonsense phosphorothioate oligodeoxynucleotide.
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PMID:Non-sequence-specific antimalarial activity of oligodeoxynucleotides. 818 11

A Plasmodium vivax-like human malaria parasite was recently identified from Madang, a holoendemic malarious region in Papua New Guinea. The complete nucleotide sequence of the circumsporozoite (CS) protein gene of this parasite is presented here. The CS protein of this parasite has an 11-mer repeat sequence and is different from the other known CS protein genes of human malaria parasites. However, it is identical to the CS protein gene of a monkey malaria parasite, Plasmodium simiovale. This P. vivax-like malaria parasite was found in Sepik, another malarious region of Papua New Guinea, and in Brazil, Indonesia, and Madagascar. No pure isolate of this parasite was identified. Specific oligonucleotide probes were used to determine relative proportion of the P. vivax-like parasite in P. vivax (type 1 and type 2) mixed field isolates. Compared with P. vivax or Plasmodium falciparum, the circumsporozoite protein of P. vivax-like parasites showed markedly less polymorphism.
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PMID:Global occurrence of Plasmodium vivax-like human malaria parasite. 824 33

Athrombospondin-related anonymous protein (TRAP) of the human malaria parasite Plasmodium falciparum shares highly conserved amino acid sequence motifs with the circumsporozoite protein of all plasmodia sequenced so far, as well as with unrelated proteins like thrombospondin and properdin. Although it was first described as an asexual blood stages protein, there has been some controversy about its expression in these stages. Pursuant to our interest in the conserved sequences within the malaria antigens, we synthesized an 18-residue peptide (18-mer) representing a conserved motif of TRAP and raised polyclonal antibodies against it. In an immunoblot assay in which we probed proteins from the asexual blood stages of the parasite, we found that this antibody recognized predominantly a 78-kDa protein in the whole parasite lysate. Furthermore, in another immunoblot, the recombinant TRAP constructs containing the conserved-motif sequence were distinctly recognized by the antipeptide antibodies, whereas a construct lacking the motif sequence was not, suggesting that the antibodies specifically cross-reacted with a protein which might be a TRAP-like protein present in the asexual blood stages of the parasite. Also, in an immunofluorescence assay, this antibody brightly stained the acetone-fixed trophozoites of the parasite. Most significantly, anti-18-mer immunoglobulin G, as well as antipeptide antibody against a smaller (nonamer) construct representing the most conserved motif within the 18-mer, inhibited the merozoite invasion of erythrocytes in a dose-dependent manner. These results provide evidence of the expression of TRAP or a TRAP-like protein in the asexual blood stages of the parasite and of a possible role of the conserved motifs in the parasite-host cell interaction during the process of invasion.
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PMID:Antibodies to a conserved-motif peptide sequence of the Plasmodium falciparum thrombospondin-related anonymous protein and circumsporozoite protein recognize a 78-kilodalton protein in the asexual blood stages of the parasite and inhibit merozoite invasion in vitro. 867 23

Three alleles of the FC27-type allelic family of the MSP2 gene of the malaria parasite Plasmodium falciparum have been sequenced from parasites from the field (The Gambia and Tanzania). These alleles lack the 12 amino acid repeat units which are usual in this family of MSP2 alleles. We have investigated the recognition by sera from an endemic area (The Gambia) of three recombinant MSP2 proteins that have 5, 1 and no copies of this repeat region. Antibody recognition of these recombinant proteins varied according to the number of repeats present. High titre antibody levels were seen with most sera using the recombinant protein with 5 x 12-mer repeats, whereas only low responses were measured using proteins containing 1 or no 12-mer repeats. Several sera entirely failed to recognise the protein which lacked 12-mer repeats. The data suggest that variation in the number of tandem repeat sequences could allow the parasite to avoid high avidity antibody binding and this may allow escape from immune recognition.
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PMID:Differential antibody recognition of FC27-like Plasmodium falciparum merozoite surface protein MSP2 antigens which lack 12 amino acid repeats. 922 95

Subcutaneous administration in mice of recombinant Sindbis viruses expressing a class I major histocompatibility complex-restricted 9-mer epitope of the Plasmodium yoelii circumsporozoite protein or the nucleoprotein of influenza virus induces a large epitope-specific CD8(+) T-cell response. This immunization also elicits a high degree of protection against infection with malaria or influenza A virus.
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PMID:Recombinant Sindbis viruses expressing a cytotoxic T-lymphocyte epitope of a malaria parasite or of influenza virus elicit protection against the corresponding pathogen in mice. 965 44

The ring-infected erythrocyte surface antigen (RESA) is a dense-granule protein of Plasmodium falciparum which binds to the cytoskeletal structure of the erythrocyte after parasite invasion. It is currently under trial as a vaccine candidate. In an effort to characterize further the antibody responses to this antigen, we have panned two independent libraries of random peptides expressed on the surface of filamentous phage with a monoclonal antibody (MAb 18/2) against RESA. One library consisted of a potentially constrained 17-mer peptide fused with the gpVIII phage coat protein, and the other displayed an unconstrained 15-mer as a fusion with the minor phage coat protein gpIII. Several rounds of biopanning resulted in enrichment from both libraries clones that interacted specifically with MAb 18/2 in protein-blotting and enzyme-linked immunosorbent assay experiments. Nucleotide sequencing of the random oligonucleotide insert revealed a common predominant motif: (S/T)AVDD. Several other clones had related but degenerate motifs. Thus, a monoclonal antibody against a malarial antigen can select common mimotopes from different random peptide libraries. We envisage many uses for this technology in malaria research.
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PMID:Isolation of peptides that mimic epitopes on a malarial antigen from random peptide libraries displayed on phage. 1045 16


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