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

We expressed two regions of the serine repeat antigen (SERA) protein of Plasmodium falciparum in Escherichia coli by synthesizing the genes with a changed codon usage. One of the synthetic gene sequences encodes amino acid residues 17-382 (SE47') and the other encodes amino acid residues 586-802 (SE50A). The products produced by the synthetic gene sequences in E. coli accounted for 15-30% of the total bacterial protein. Antisera against both the purified gene products prepared in rats inhibited malaria parasite growth in vitro. The anti-SE47' serum was significantly more inhibitory than the anti-SE50A serum. The described methods provide a large scale preparation of recombinant antigens for improving and producing malaria vaccine.
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PMID:Production of recombinant SERA proteins of Plasmodium falciparum in Escherichia coli by using synthetic genes. 887 4

Recently it has become evident that he same candidate antigen can be shared by several of the parasite stages, and thus the concept of a multistage vaccine is becoming more and more attractive. A TDR Task Force evaluated the promise and stage of development of some 20 existing asexual blood stage candidate antigens and prepared a strategy for their development leading to clinical testing and field trials, Amongst these are merozoite surface protein 1 (MSP-1), Serine Rich Antigen (SERA), Apical Membrane Antigen (AMA-1), and Erythrocyte Binding Antigen (EBA). A field study conducted in Tanzanian children showed that the SPf66 Colombian vaccine was safe, induced antibodies, and reduced the risk of developing clinical malaria by around 30%. This study, confirmed the potential of the vaccine to confer partial protection in areas of high as well as low intensity of transmission. Pfs25 is a leading candidate antigen for a transmission blocking vaccine. It is found in the ookinete stage of the parasite in the mosquito midgut. Gramme amounts of GMP-grade material have been produced and a vaccine based on the Pfs25 antigen formulated with alum should have gone into phase I and II clinical trials in the USA and Africa during 1995. Because the first malaria prototype vaccine to be tried out in people on a large scale has been the polymerized synthetic peptide developed by patarroye on the basis of the SPf66 antigen of P. faliciparum, the results are with much interest. It is still premature to predict the effectiveness of this vaccine globally, but its development will encourage further progress in a fields that has repeatedly been characterized by raised and then dashed drops. These various vaccines are based on the classical approach to vaccination, which is to raise host immunity against the parasite so as to reduce parasite densities or to sterilize an infection. A newer approach is development of antidisease vaccines which aim to alleviate morbidity by suppressing immunopathology in the host. Antidisease vaccines are based on neutralizing parasite components that induce host pathology, leaving the parasite itself directly unaffected. These effects would occur when each type of the disease is considered by it self; however, synergistic effects may be expected when they are used in combination. The rational for vaccines based on any of these stages was that immunization of various hosts with whole parasites of each of these stages has been able to induce protection or total transmission-blocking immunity. Less significant but not to be discounted is the fact that natural malaria infections in humans have been shown to induce immunity against every one of these parasite stages against which vaccines are being developed, an exception to this are those stages that are present only in the mosquito vector with component molecules not presented to the human host, such as exclusively ookinete antigens. For several very apparent reasons a vaccine today is conceived of as subnit as opposed to show1 parasite vaccines, either in the form of a recombinant product or as synthetic peptide constructs. Genes coding for several antigens of P. falciparum and some of P. vivax have been seems to be common to many Plasmodium antigens; this is that they contain tandem repeats of oligopeptide sequences which often code for immunodominant epitopes. Following several decades of research on malaria vaccine development, the field at a glace may present a conflicting picture, with several achievements, and some disappointments and controversies. Issues facing the development of a malaria vaccine are complex. It is not clear how far we may yet be from achieving this goal. The work of the past decades has laid an extensive foundation of ralevant knowledge and technologies, and the goal it self remains as important as ever, will scientists remain committed to this objective?
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PMID:Malaria vaccine. 900 71

Previously, the Plasmodium falciparum serine repeat antigen has been shown to be protective in primate models of malaria immunity and also to be a target of in vitro parasite-inhibitory antibodies. To further define parasite-inhibitory epitopes a series of deletions from the amino-terminal 47-kDa domain of the serine repeat antigen (SERA) were constructed as glutathione-S-transferase fusion proteins. Several GST-SERA fusion proteins were used to vaccinate mice with Freund's adjuvant and the resulting immune sera were used to assay for the inhibition of P. falciparum invasion of erythrocytes in vitro. The minimal epitope shown to be the target of invasion-blocking antibodies was SERA amino acids 17-165. Additional GST-SERA deletion constructs of the 47-kDa domain were developed and evaluated for reactivity, by Western immunoblot analysis, with a parasite-inhibitory murine monoclonal antibody (mAb 43E5), a parasite-inhibitory pooled goat polyclonal sera, and a pooled human Nigerian immune serum. The parasite-inhibitory epitope defined by mAb 43E5 was mapped to SERA amino acids 17-110 and, at least, part of the epitope was defined to include amino acids in the region of amino acids 59-72. The parasite-inhibitory epitope recognized by mAb 43E5 appears to be well conserved between diverse geographical isolates of P. falciparum. The results have relevance for malaria vaccine development and suggest that an appropriately designed recombinant SERA antigen produced from a synthetic gene in Escherichia coli may be an effective component of a candidate malaria vaccine.
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PMID:Plasmodium falciparum: an epitope within a highly conserved region of the 47-kDa amino-terminal domain of the serine repeat antigen is a target of parasite-inhibitory antibodies. 903 Jun 63

Infection of human erythrocytes with the malaria parasite Plasmodium falciparum induces many morphological and biochemical changes in the host cell. Host serine/threonine protein kinases could be involved in some of these processes. The aim of this study was to determine the effect of infection on red blood cell protein kinase C (PKC) and establish the importance of this enzyme in parasite growth and sexual stage differentiation. Phorbol myristate acetate (PMA)-induced translocation of erythrocyte PKC activity is impaired in erythrocytes enriched for mature asexual stage infected cells. Western blotting shows that this is due to a relative reduction in membrane PKC protein levels rather than inhibition of enzyme activity and analysis of PKC activity isolated from whole cell lysates by DE52 chromatography suggests that total activatable PKC levels are lower in infected erythrocytes. A reduction in PMA-induced activation is also observed in PKC assays performed in situ. Downregulation of erythrocyte PKC by overnight incubation with PMA before infection causes a significant decrease in the rate of the asexual growth, suggesting that the enzyme, although lost later in infection, may be important in the earlier development of the parasite. By contrast, the lack of PKC had no effect on the production of sexual stage parasites.
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PMID:Modulation of protein kinase C activity in Plasmodium falciparum-infected erythrocytes. 905 62

The nucleotide and deduced amino acid sequence of a serine protease (AgSp24D) from the human malaria vector, Anopheles gambiae, is presented. The gene product is a 271 amino acid protein that contains the conserved serine, histidine and aspartic acid residues found in serine proteases, and has the highest identity to a serine protease of unknown function from Drosophila melanogaster. In situ hybridization to the polytene chromosomes detects a single band at 24D. Northern analysis reveals only low levels of transcripts in larvae and pupae, but more abundant transcription products occur in adults. Interestingly, this analysis also shows that adult males express much higher levels of AgSp24D mRNA than females. In addition, Plasmodium-refractory mosquitoes express higher levels of AgSp24D mRNA than susceptible mosquitoes although the biological significance of this remains to be examined. The thorax is the primary site for expression in the adults. The lack of a dramatic increase in AgSp24D mRNA levels following blood feeding suggests that this protease is not involved in digestive processes. Transcriptional induction does not follow cold shock, septic wounding, bacterial injection, laminarin injection or CM-Sephadex bead injection.
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PMID:Cloning and characterization of a serine protease from the human malaria vector, Anopheles gambiae. 935 80

Chitinases that function in the molting of the larval exoskeleton have been characterized previously. However, chitinase expression in an adult insect gut has not been described. Here we report on the initial characterization and cloning of a novel chitinase gene that is expressed specifically in the midgut of adult Anopheles gambiae females. Upon feeding, chitinase is secreted into the gut lumen as an inactive pro-enzyme that is later activated by trypsin. Thus, temporal regulation of chitinase activity is tightly coupled to the temporal pattern of trypsin secretion. The enzyme may play a role in structuring the chitin-containing extracellular peritrophic matrix, whose formation is also induced by feeding. A chitinase cDNA was cloned from a library enriched for gut-specific sequences. The open reading frame encodes a 525-amino acid protein comprised of a putative catalytic domain at the N terminus, a putative chitin-binding domain at the C terminus, and a threonine/serine/proline-rich amino acid stretch in between them. Northern analysis indicates that this chitinase is expressed exclusively in the guts of adult females and not in adult carcasses or in any larval or pupal tissues. The present findings suggest the possibility of using this chitinase as an antigen for a malaria transmission-blocking vaccine.
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PMID:Characterization of a novel gut-specific chitinase gene from the human malaria vector Anopheles gambiae. 936 Sep 58

Protein phosphatases play a critical role in the regulation of the eukaryotic cell cycle and signal transduction. A putative protein serine/threonine phosphatase gene has been isolated from the human malaria parasite Plasmodium falciparum. The gene has an unusual intron that contains four repeats of 32 nucleotides and displays a high degree of size polymorphism among different strains of P. falciparum. The open reading frame reconstituted by removal of the intron encodes a protein of 466 amino acids with a predicted molecular mass of approximately 53.7 kDa. The encoded protein, termed protein phosphatase beta (PP-beta), is composed of two distinct domains. The C-terminal domain comprises 315 amino acids and exhibits a striking similarity to the catalytic subunits of the type-2A protein phosphatases. Database searches revealed that the catalytic domain has the highest similarity to Schizosaccharomyces pombe Ppa1 (58% identity and 73% similarity). However, it contains a hydrophilic insert consisting of five amino acids. The N-terminal domain comprises 151 amino acid residues and exhibits several striking features, including high levels of charged amino acids and asparagine, and multiple consensus phosphorylation sites for a number of protein kinases. An overall structural comparison of PP-beta with other members of the protein phosphatase 2A group revealed that PP-beta is more closely related to Saccharomyces cerevisiae PPH22. Southern blots of genomic DNA digests and chromosomal separations showed that PP-beta is a single-copy gene and is located on chromosome 9. A 2800-nucleotide transcript of this gene is expressed specifically in the sexual erythrocytic stage (gametocytes). The results indicate that PP-beta may be involved in sexual stage development.
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PMID:Protein phosphatase beta, a putative type-2A protein phosphatase from the human malaria parasite Plasmodium falciparum. 936 59

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

The Plasmodium falciparum serine repeat antigen (SERA) and serine repeat protein homologue (SERPH) contain highly conserved domains that appear to encode cysteine proteases or related proteins. Humoral immune responses against the protease domains of SERA and SERPH were evaluated. Malaria-immune Africans, but not nonimmune controls, demonstrated potent humoral responses against the protease domains. As the SERA and SERPH protease domains are likely accessible to circulating antibody, these results suggest that humoral responses to the domains may contribute to antimalarial immunity.
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PMID:Humoral immune responses of Africans to cysteine protease-related antigens of Plasmodium falciparum. 965 57

The Plasmodium falciparum proteins serine repeat antigen (SERA) and serine repeat protein homologue (SERPH) have similarity in sequence with cysteine proteases in a well-conserved protease domain. We identified three SERA homologues from the murine malaria parasite Plasmodium vinckei and evaluated immune responses to the protease domains of these proteins. Mice that developed protective immunity to P. vinckei after serial infection and cure demonstrated humoral and cell-mediated responses against the SERA homologue protease domains. Mice immunized with Salmonella typhimurium expressing the protease domain of one of these antigens demonstrated cellular responses against the antigen and increased survival against lethal challenge with P. vinckei. Our results suggest that the protease domains of SERA and SERPH are worthy of additional study as potential components of a malaria vaccine.
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PMID:Protective immune responses against protease-like antigens of the murine malaria parasite Plasmodium vinckei. 968 79


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