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)

The late blood stages of the human malaria parasite, Plasmodium falciparum, carry a major surface antigen, p190, of molecular weight (Mr) 190,000. This antigenically variable protein is actively processed, first as the parasite matures and again when it is released into the blood stream and invades a new erythrocyte to initiate a cycle of growth. It elicits a strong immune response in man; all tested adult sera from endemic areas have antibodies against this protein. Our evidence indicates that purified p190 can alter the course of parasitaemia in monkeys with falciparum malaria. We have also succeeded in cloning part of the gene for p190 and expressing it in Escherichia coli. To this end we have developed a new technique, antibody select, which greatly simplifies final identification of expressing clones.
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PMID:Major surface antigen gene of a human malaria parasite cloned and expressed in bacteria. 609 Sep 34

A detailed analysis of P190, a major surface associated protein of Plasmodium falciparum erythrocytic stages has been undertaken. We have demonstrated that this protein is recognised by two monoclonal antibodies, one of which recognises a constant feature (2.2) and one a variable feature (7.3). Cell free protein synthesis demonstrates that the variable 7.3 epitope is encoded in the structural gene for P190. The 7.3 epitope is only present on late trophozoites and schizonts whilst the 2.2 epitope is present on all erythrocytic stages. Labelling of synchronised cultures demonstrates that P190 is made only from 30 h onwards, (i.e. by trophozoites and schizonts). By pulse chase analysis we show that P190 undergoes processing and is lost at release/re-invasion, correlating with a lack of 7.3 immunofluorescence reactivity on rings. Sera from Nigeria recognise P190 from a Thai isolate of malaria. They also react with purified P190 in a micro-ELISA assay. A model for the role of P190 in re-invasion is presented, and the possible clinical significance of this protein is discussed.
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PMID:Processing, polymorphism, and biological significance of P190, a major surface antigen of the erythrocytic forms of Plasmodium falciparum. 620 67

The p190 protein (also called MSA1 or MSP1) of the asexual blood stage forms of Plasmodium falciparum, a human malaria vaccine candidate, shows polymorphism between different isolates. Mice were immunized with p190-3, a recombinant protein which contains mostly conserved sequences derived from the p190 protein of the K1 parasite isolate. Proliferative T-cell responses of lymph node cells from immunized mice were assessed by stimulation in vitro with p190-3 or preparations of parasitized red blood cells (PRBC) containing the native protein. The p190-3-specific T cells from C57BL/6 mice consistently responded to some P. falciparum isolates, representing either the K1 or MAD20 serotype of p190, but not to other P. falciparum strains or to rodent malaria parasite-infected red blood cells. p190-3-specific T-cell responses from other mouse strains (BALB/c, C3H/He) did not distinguish between P. falciparum isolates. The polymorphic epitopes which were preferentially recognized by T cells from C57BL/6 mice were identified.
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PMID:Identifying polymorphic regions of the p190 protein from different Plasmodium falciparum strains by using specific T cells. 768 80

Immune responses of 97 Gambian women and their neonates were studied. New methods distinguished between active and previous placental malaria, were used to examine relationships between maternal malaria and neonatal immune responses. Many placentas (61%) had active or previous malarial infection. Maternal and cord malarial IgG levels correlated (P < 0.001). Malarial IgG was raised in cord blood in active placental malaria; IgM was not detected. Mean lymphoproliferation and the proportion of responders to soluble P. falciparum antigens (F32) and conserved regions of p190 expressed on trophozoites and schizonts (190L and 190N) were higher in neonates than mothers. There was no clear relationship between maternal malaria and neonatal mean lymphoproliferation to malarial antigens, although fewer neonates responded when mothers were actively infected. Matched maternal and neonatal lymphoproliferation responses did not correlate. However, first born neonatal lymphoproliferation to PPD and malarial antigens appeared lower than other neonates, in agreement with lower lymphoproliferation in primigravidae compared with multigravidae. Also in common with mothers, autologous plasma suppressed neonatal lymphoproliferation to PPD and malarial antigens, suggesting common immunoregulation. Higher cortisol or other circulating factors in first pregnancies may be implicated. The relevance of cell-mediated malarial immune responses detected at birth remains to be established.
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PMID:Relationships between maternal malaria and malarial immune responses in mothers and neonates. 773 30

A DNA fragment, designated as P190TR, encoding amino acid residues of the tripeptide region of the P190 antigen was amplified by polymerase chain reaction from genomic DNA of FCC1/HN Plasmodium falciparum isolated from Hainan Province, China. Upon comparison with the nucleotide sequences of MAD20 allele, it was found that there were five bases substitution in the P190TR which cause amino acid changes. The DNA fragment sequenced were ligated to BamHI and XbaI-digested pGEX-2T vector. Competent E. coli JM109 (DE3) were transformed with either parental or recombinant pGEX-2T for expression. Analysis of soluble cellular proteins revealed the high level expression of GST-P190TR as fusion proteins. Affinity purification of the fusion protein under nondenaturing condition resulted in the removal of almost all other E. coli proteins. The purified P190TR protein was highly immunogenic in rabbits. The antibodies against the recombinant protein recognized the malaria parasite with the titers at 1:320 measured by IFA and antisera from malarial patients reacted with the expressed protein in Western Blot.
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PMID:Expression and immunogenicity of tripeptide repeat region on P190 of Plasmodium falciparum. 778 21

Among Tanzanian children living in an area of intense and perennial malaria transmission, prevalence of naturally acquired IgG antibodies that recognize SPf66, NANP, p190 and a 19 kDa fragment of the merozoite surface protein-1 (MSP-1) is high and increases with age. This possibly reflects the high level of natural exposure of the children to P. falciparum. The prevalences of IgG antibodies that recognize the three putative merozoite derived sequences contained in the malaria vaccine SPf66 (83.1, 55.1 and 35.1) is low but also show some age dependence. Three doses of the SPf66 vaccine induce a strong IgG antibody response against both the SPf66 construct, NANP and the three individual peptides. Vaccination with SPf66 did not result in an increase of anti19 kDa fragment antibodies. This reflects the specificity of the humoral immune response induced by the SPf66 construct. Among vaccinated children, antibody titres against SPf66 decreased over time following the third dose. However, 18 months after the third dose, SPf66 recipients still had significantly higher IgG titres and stimulation indices of peripheral blood mononuclear cells (PBMC) than placebo recipients. Within the vaccine group, there is a trend for increasing anti-SPf66 IgG titre to be associated with decreasing risk of clinical malaria but this was not statistically significant. Results also show the difficulties of establishing whether antibody responses are related to protection in field trials in endemic areas.
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PMID:Immune responses to Plasmodium falciparum antigens during a malaria vaccine trial in Tanzanian children. 957 49

Serum immunoglobulin (Ig)G1, IgG3 and total IgG were assessed by immunoabsorbent assay in 198 infants from a Tanzanian village highly endemic for Plasmodium falciparum. Antibodies were measured against epitopes of the circumsporozoite protein (the repetitive epitope (NANP)50 and a construct of the flanking regions (CS27IC)), the malaria vaccine SPf66, and two constructs of the merozoite surface protein-1 (MSP-1), a 19-kDa fragment from the C-terminal domain (MSP-119) and an N-terminal fragment spanning blocks 1-6 (H6-p190 M-1/6-H6). IgG1 and total IgG titres showed similar age profiles, all decreasing for the first 2 months of life. Anti-(NANP)50 titres remained very low throughout the first year of life, while anti-CS27IC antibody appeared to peak around 7 months of age. Only a slight tendency to increase with age was observed for levels of the other antibodies studied. IgG3 titres except for H6-p190(1/6), were very low initially and remained very low throughout the first year of life. Clinical malaria incidence at the village dispensary was analysed prospectively in relation to antibody. No IgG1 or total IgG titre showed protective effects, but low IgG3 against p190(1/6) appeared to be a risk factor in some age groups. Given the large number of antibodies tested, this single indication of possible protection could merely be chance. There were no strong associations between antibody titres and entomologically assessed sporozoite exposure suggesting that transmission-reducing interventions may have little effect on antibody levels in such children.
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PMID:Antibodies against Plasmodium falciparum vaccine candidates in infants in an area of intense and perennial transmission: relationships with clinical malaria and with entomological inoculation rates. 1035 53


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