Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0024530 (malaria)
 44,886 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A library of cDNA clones expressing antigens of the asexual blood-stages of Plasmodium falciparum (isolate FCQ27/PNG) was constructed in the bacteriophage vector gamma gt11-Amp3. Clones expressing P. falciparum antigens (as polypeptides fused to beta-galactosidase) were selected by their reactivity in an in situ colony immunoassay with affinity-purified malaria antibodies. A detailed analysis of 78 antigen-positive clones selected from approximately 10,000 recombinant clones has shown them to correspond to many different parasite antigens. cDNA hybridization studies on this array of 78 antigen-positive clones have so far identified 18 families of sibling clones with 22 clones as yet unassigned, the majority of which may represent additional unique sequences. Only about 20% of the clones synthesized abundant amounts of the malaria antigen/beta-galactosidase fused polypeptide but each multi-member family except one was represented by at least one clone producing a fused polypeptide in abundance. Antisera have been raised against cloned malaria antigens by immunizing mice and rabbits with bacterial lysates and purified fused polypeptides, respectively. These antisera have been used to characterize the antigens in P. falciparum that correspond to the various antigen-positive clones. The variety of distinct antigens recognized by these antisera confirms that the clone library contains coding sequences for many different antigens.
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PMID:Plasmodium falciparum complementary DNA clones expressed in Escherichia coli encode many distinct antigens. 639 47

During acute malaria infection, platelets in human platelet-rich plasma re hypersensitive to the addition of ADP between 1.0 micro M and 5.0 micro M, or adrenaline 0.11 micro M as aggregating agents. The mean maximum aggregation amplitude (as % of light transmission) obtained from 8 subjects in response to added ADP (1.0 micro M) , 39.8 +/- 27 (1SD), was significantly greater than the value in 6 controls (5.2 +/- 6.7 (1SD); t = 3,51 P less than 0.005). A similar pattern of response was obtained with higher ADP concentrations (2,4, 4.5 or 5.0 micro M) in 22 patients and 20 control subjects (89.9 +/- 14.9 % vs 77.8 +/- 16.5% (1SD) t = 2,45, P less than 0.02). Addition to 4.5 microM ADP to patient PRP usually evoked only a single aggregation wave (fused primary and secondary waves) while the typical primary and secondary wave pattern was usually obtained from controls. Mean plasma B-thromboglobulin (BTG) concentration in 7 patients (208.3 +/0 15.6 ng/ml) was significantly higher than the value in 6 control subjects (59.2 +/- 15.7 ng/ml; t=13.44, P less than 0.002).
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PMID:Platelet hypersensitivity in acute malaria (Plasmodium falciparum) infection in man. 645 13

Spleen cells of BALB/c mice that were immune to the 17X strain of P. yoelii were fused with P3X63Ag8 myeloma cells. Two hundred fifty-three of 1053 hybrid cells produced antibodies reactive with disrupted 17X parasites in a solid phase radioimmunoassay. One of these antibodies, McAb 302, reacted with the merozoites of the 17X (nonlethal) and 17XL (lethal) variants of P. yoelii. Of greater significance, McAb 302 passively protected mice against challenge infection with the lethal variant. Mice treated with this antibody before infection developed low-grade parasitemia (less than 0.3%) of short duration when challenged with P. yoelii 17XL . In contrast, control mice that had been untreated or injected with ascites fluid lacking McAb 302 uniformly died with fulminating malaria upon challenge with the same parasite. In other experiments, McAb 302 was shown capable of controlling blood parasite levels when administered to mice with patent P. yoelii 17XL infections. Although all control mice died, mice protected with a single dose of McAb 302 ultimately cleared their infections. Regardless of how passive immunization was performed, mice given McAb 302 were resistant to subsequent challenge with P. yoelii 17XL , indicating they had developed significant immunity during their initial controlled infections. McAb 302 also showed pronounced passive protective activity against the nonlethal 17X strain of P. yoelii, which is a parasite of reticulocytes. The protection afforded by McAb 302 was specific, because mice passively immunized with this antibody died when challenged with the unrelated P. vinckei. McAb 302 was shown to possess the IgG3 isotype and precipitated a 230-kd protein plus several smaller polypeptides from metabolically labeled parasite antigen preparation derived from both variants of P. yoelii. It did not react with similar preparations of other murine plasmodial species.
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PMID:Passive immunization against murine malaria with an IgG3 monoclonal antibody. 672 50

Soluble plasma antigens in 53 Liberian patients with P. falciparum malaria were analyzed in double diffusion using plasma from 27 immune adults. One immune plasma reacted with 17% of the plasma samples and was used in subsequent quantitative immunoelectrophoretic (IE) studies as antiserum. By fused rocket IE 2 antigens were found in samples with parasitaemia (P) above 0.6% and above 4.5% P the antigens had grossly increasing concentration. In 22 samples of 0.6% P or more, 7 antigens were demonstrated by crossed IE. Two electrophoretically heterogeneous antigens. Ag-1 and Ag-2, were found most frequently. Ag-1 was partly heat-stable and was in some samples amphiphilic as shown by charge shift crossed IE. Ag-1 and Ag-2 did not contain integral erythrocyte membrane proteins, and Ag-1 is suggested to be a structural protein of P. falciparum. Twenty-six immune plasma samples were screened for antibodies against 4 antigens in crossed IE with intermediate gel. It is suggested that an index for protective immunity may be obtained by summation of semiquantitative titers obtained by crossed IE with intermediate gel using an antigen pool representing e.g. 20--30 soluble antigens.
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PMID:Antigens and antibodies in Plasmodium falciparum malaria studied by immunoelectrophoretic methods. 678 Dec 21

We have reported previously that immunization with a bacterial recombinant protein containing the two epidermal growth factor (EGF)-like modules of Plasmodium yoelii Merozoite Surface Protein-1 (MSP-1) protected mice against challenge with this malaria parasite. Bacterial plasmids containing sequences coding for the individual modules fused to glutathione S-transferase (GST) have now been made. The fusion protein containing the combined EGF-like modules was recognized by anti-parasite antibodies and was immunogenic, producing high titre anti-parasite and anti-GST antibodies. In contrast, fusion proteins containing the two individual EGF-like modules reacted poorly with the natural antibodies and their proteins, as well as a simple mixture of them, induced low levels of anti-parasite antibodies despite producing high levels of anti-GST antibody. Antibodies raised to the recombinant proteins recognized the 230 kDa MSP-1. Groups of mice immunized with the different recombinant proteins were challenged with parasites: protection was observed in the group which had received the recombinant protein containing both modules but not in those groups immunized with the individual modules, either alone or as a mixture. These results suggest that there are important structural determinants formed by the two modules together, which are not present in either of the individual domains alone, and which are responsible for the immunogenicity of the protein or are the target of protective antibodies.
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PMID:The combined epidermal growth factor-like modules of Plasmodium yoelii Merozoite Surface Protein-1 are required for a protective immune response to the parasite. 750 23

The "carrier effect," defined as the provision of T cell recognition sites physically linked to B cell epitopes in order to provide Th cell function for antibody synthesis, is well known. Peptides, proteins, and more recently particulate protein antigens have been used for this purpose. The hepatitis B core antigen represents a highly immunogenic antigen in humans as well as in experimental animal models. Studies in mice have provided insight into this enhanced immunogenicity. For example, HBcAg directly activates B cells (i.e., T cell independence), HBcAg elicits strong T cell responses, and HBcAg is efficiently processed and presented by antigen presenting cells (APCs). These characteristics suggested that HBcAg may be an ideal carrier moiety for B cell epitopes requiring additional Th cell function. Therefore, a number of HBV and non-HBV B cell epitopes have been chemically linked or fused by recombinant methods to HBcAg as a method to increase immunogenicity with significant success. We have designed bacterial expression vectors that allow insertion of heterologous B cell epitopes at various positions within HBcAg particles and permit efficient purification of hybrid HBcAg particles. Studies of positional effects have demonstrated that an internal insertion into a dominant HBcAg-specific B cell site represents a superior location for enhanced antibody production. Immunogenicity studies have been extended to protection against experimental challenge in several systems. For example, a malaria CS repeat sequence derived from P. berghei was inserted into HBcAg at the internal site, and purified hybrid HBcAg/CS particles were highly immunogenic and protected 100% of experimentally challenged BALB/c mice. This system has also been exploited for purposes of oral vaccination by expressing genes coding for hybrid HBcAg particles in live, avirulent vaccine strains of Salmonella species.
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PMID:The hepatitis nucleocapsid as a vaccine carrier moiety. 754 55

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.
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PMID:Human immune recognition of recombinant proteins representing discrete domains of the Plasmodium falciparum gamete surface protein, Pfs230. 773 31

This paper provides a review on the development of hepatitis core antigen as a vaccine carrier moiety and the use of recombinant Salmonella vaccine strains expressing hybrid HBcAg particles as live oral vaccines. Salmonella spp. can be attenuated by defined genetic means so that they become avirulent, yet preserve invasiveness after oral uptake. Oral immunization of mice with such avirulent candidate Salmonella typhimurium vaccine strains elicited serum antibody responses against a limited number of bacterial antigens. A highly immunogenic viral nucleocapsid antigen, hepatitis B virus core antigen (HBcAg) that can be expressed in prokaryotes was used as a carrier moiety for B-cell epitopes. Insertion sites with an enhanced immunogenicity for the carried epitopes were defined using HBV envelope protein virus neutralizing epitopes. An internal insertion site in HBcAg was found that drastically enhanced the immunogenicity of the foreign (pre-S1) epitope while reducing the immunogenicity of the carrier protein. Internally fused HBc/pre-S hybrid particles were expressed in Salmonella typhimurium and S. typhi vaccine strains. A single oral immunization of mice with such live recombinant S. typhimurium strains elicited a high titred serum anti-pre-S1 IgG response. Similarly, circumsporozoite repeat epitopes of three different malaria parasites were expressed as HBcAg/CS hybrids in recombinant S. spp. and were found to be highly immunogenic.
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PMID:Development of recombinant Salmonellae expressing hybrid hepatitis B virus core particles as candidate oral vaccines. 795 69

Mefloquine is currently the drug-of-choice for malaria prophylaxis among military personnel. Four active duty military personnel receiving 250 mg mefloquine per week were killed in the line of duty under combat conditions. Samples of blood, bile, liver, kidney, muscle, brain, spleen and lung were submitted to the Division of Forensic Toxicology, Office of the Armed Forces Medical Examiner, for routine toxicologic analysis. Qualitative screening revealed only the presence of ethanol (< 25 mg/dl, probably attributable to postmortem formation) and mefloquine. Quantitation of mefloquine was performed using an HP 5880 gas chromatograph equipped with a nitrogen/phosphorus detector. The column was an HP-5 cross-linked 5% phenyl methyl silicone fused silica capillary column (15 m x 0.25 mm i.d. x 0.25 microns film thickness). The temperature program began at 110 degrees C, was held for 1 min and ramped at 20 degrees C/min to 200 degrees C, held for 1 min and then ramped at 10 degrees C/min to 280 degrees C and held for 10 min. Mefloquine elutes with a relative retention time similar to that of the tricyclic antidepressants. No postmortem data concerning mefloquine concentrations or tissue distribution was available. Quantitated blood concentrations in the presented cases were greater than the expected therapeutic values indicating the possibility of postmortem redistribution of this drug. No mefloquine overdoses were identified in the literature making comparison to the postmortem therapeutic concentrations impossible at this time.
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PMID:Mefloquine distribution in postmortem cases. 795 78

We have expressed in bacteria the C-terminal part of Plasmodium yoelii merozoite surface protein-1 (MSP1) containing the two epidermal growth factor-like domains. The protein, either alone or fused to glutathione S-transferase, was highly effective as a vaccine and protected mice against challenge infection. Reduction and alkylation abolished the protection obtained with the protein. This shows for the first time the absolute requirement of the disulphide-bonded conformation for immunogenicity. In a short term experiment, mice were protected against a massive challenge. The immunity was effective at the time of merozoite release/reinvasion. Recombinant protein based on this part of MSP1 may be suitable as a vaccine against malaria.
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PMID:Immunization against malaria with a recombinant protein. 801 56


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