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)

Merozoite surface protein-1 (MSP-1, also referred to as P195, PMMSA or MSA 1) is one of the most studied of all malaria proteins. The protein is found in all malaria species investigated and structural studies on the gene indicate that parts of the molecule are well-conserved. Studies on Plasmodium falciparum have shown that the protein is in a processed form on the merozoite surface, a result of proteolytic cleavage of the large precursor molecule. Recent studies have identified some of these cleavage sites. During invasion of the new red cell most of the MSP1 molecule is shed from the parasite surface except for a small C-terminal fragment which can be detected in ring stages. Analysis of the structure of this fragment suggests that it contains two growth factor-like domains that may have a functional role.
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PMID:A malaria merozoite surface protein (MSP1)-structure, processing and function. 134 16

The protective efficacy of several recombinant and a synthetic Plasmodium falciparum protein was assessed in Aotus monkeys. The rp41 aldolase, the 190L fragment of the MSA-1 protein and fusion 190L-CS. T3 protein containing the CS.T3 helper "universal" epitope were emulsified in Freund's adjuvants and injected 3 times in groups of 4-5 monkeys each one. The synthetic polymer Spf (66)30 also emulsified in Freund's adjuvants was injected 6 times. Control groups for both experiments were immunized with saline solution in the same adjuvant following the same schedules. Serology for malaria specific antibodies showed seroconversion in monkeys immunized with the recombinant proteins but not in those immunized with the polymer nor in the controls. Challenge was performed with the 10(5) parasites from the P. falciparum FVO isolate. Neither rp41 nor Spf(66)30 induced protection, whereas 190L induced significant delay of parasitemia. The fusion of the CS.T3 epitope to 190L significantly increased its protective capacity.
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PMID:Efficiency of human Plasmodium falciparum malaria vaccine candidates in Aotus lemurinus monkeys. 134 22

DNA sequences of alleles at the merozoite surface antigen-1 (MSA-1) gene locus of the malaria parasite Plasmodium falciparum show evidence of repeated past recombination events between alleles. These include both (1) nonreciprocal recombination events that have homogenized certain gene regions among alleles and (2) reciprocal recombination events that have combined allelic segments with divergent evolutionary histories, thereby enhancing allelic diversity. In three different gene regions, the rate of nonsynonymous nucleotide substitution significantly exceeds that of synonymous nucleotide substitution, implying that positive Darwinian selection has acted to diversify alleles at the amino acid level. The MSA-1 polymorphism seems to be quite ancient; the two major allelic types have been maintained for approximately 35 Myr.
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PMID:Positive selection and interallelic recombination at the merozoite surface antigen-1 (MSA-1) locus of Plasmodium falciparum. 158 9

There are several mechanisms responsible for the extensive antigenic diversity found in the asexual blood stages of Plasmodium falciparum. Failure to express antigens is a feature of many isolates cultured in vitro but probably is not a major cause of antigenic diversity in vivo. Numerous point mutations occur in allelic forms of asexual blood stage antigens and are assumed to contribute to antigenic diversity but as yet few such mutations have been mapped to antigenic epitopes. A major cause of antigenic diversity is the expression of different repetitive sequences in allelic forms of several antigens including the S-antigen and the two merozoite surface antigens, MSA-1 and MSA-2. The sequencing data indicates that S-antigen genes fall into many allelic families whereas both MSA-1 and MSA-2 are dimorphic. Further diversity has arisen as a result of intragenic recombinations between the dimorphic forms of both MSA-1 and MSA-2. In addition to this diversity reflecting the expression of different allelic genes, asexual blood stages of malaria parasites undergo antigenic variation in that clonal parasite populations can vary the form of an antigen on the surface of infected erythrocytes. Antibodies or DNA probes directed against variable repeat sequences can be used to distinguish different isolates of P. falciparum. The use of antibodies to S-antigen repeats has been particularly useful for typing the parasites causing infections. The application of S-antigen typing to field studies in Papua New Guinea has demonstrated marked diversity in the parasites causing infections in one area.
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PMID:Antigenic diversity in Plasmodium falciparum. 182 Jul 15

Merozoite surface antigen MSA-2 of the human parasite Plasmodium falciparum is being considered for the development of a malaria vaccine. The antigen is polymorphic, and specific monoclonal antibodies differentiate five serological variants of MSA-2 among 25 parasite isolates. The variants are grouped into two major serogroups, A and B. Genes encoding two different variants from serogroup A have been sequenced, and their DNA together with deduced amino acid sequences were compared with sequences encoded by other alleles. The comparison shows that the serological classification reflects differences in DNA sequences and deduced primary structure of MSA-2 variants and serogroups. Thus, the overall homologies of DNA and amino acid sequences are over 95% among variants in the same serogroup. In contrast, similarities between the group A variants and a group B variant are only 70 and 64% for DNA and amino acid sequences, respectively. We propose that the MSA-2 protein is encoded by two highly divergent groups of alleles, with limited additional polymorphism displayed within each group.
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PMID:Structural and antigenic polymorphism of the 35- to 48-kilodalton merozoite surface antigen (MSA-2) of the malaria parasite Plasmodium falciparum. 199 Feb 94

Antigens associated with the surface of merozoites of the malaria parasite Plasmodium falciparum are directly accessible to immune attack and therefore are prime vaccine candidates. We have previously shown that one of the two known merozoite surface antigens (merozoite surface antigen 2; MSA-2) exhibits considerable sequence and antigenic diversity in different isolates. The sequences of MSA-2 from three isolates revealed a central domain composed of repeats that vary in number, length, and sequence, flanked in turn by nonrepetitive variable sequences and by conserved N- and C-terminal domains. We report here the sequences of a further four MSA-2 alleles, containing repetitive sequences that are related but not identical to each other. The seven alleles of MSA-2 can be divided into two distinct allele families on the basis of nonrepetitive sequences. Hybridization studies with repeat probes indicated that all of the 44 P. falciparum isolates examined contained repeat regions similar to those defined in known MSA-2 sequences.
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PMID:Structural diversity in the Plasmodium falciparum merozoite surface antigen 2. 200 Mar 83

This study was part of a larger program to develop a vaccine effective against Plasmodium falciparum infection caused by sporozoites and clinical malaria caused by asexual blood stages. In a phase 1 study of safety and immunogenicity, two recombinant proteins (Ro 46-2717, a circumsporozoite [CS] protein) construct with a molecular mass of 35 kD, and Ro 46-2924, a merozoite surface antigen [MSA-2] construct with a molecular mass of 25 kD) adsorbed onto alum were injected in two low (20 micrograms) or two high (100 micrograms) doses in the right and left deltoid muscles of 33 healthy Swiss volunteers; six other volunteers received a placebo (alum alone). Twenty-six participants reported 51 immunization-related adverse events, mainly pain at the injection site. Mean antibody titers to CS protein and MSA-2 in an indirect immunofluorescence assay peaked four weeks after the second immunization without evidence of boosting (i.e., sharp increase in titer). By that time, 56% and 31% of the vaccinees seroconverted to CS protein and MSA-2, respectively, with the increase in MSA-2 titer being weaker than that for the CS protein. After a third immunization, five vaccinees volunteered to be challenged by three or four infective bites of Anopheles stephensi. Prepatent and incubation periods in all five were comparable with unvaccinated historic controls challenged under similar conditions, and all had symptoms of clinical falciparum malaria. We conclude that the vaccine components were safe and immunogenic but there was no evidence that this immunization regimen with the CS protein plus MSA-2 component was able to prevent infection.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Safety, immunogenicity, and pilot efficacy of Plasmodium falciparum sporozoite and asexual blood-stage combination vaccine in Swiss adults. 748 98

Two synthetic polypeptides containing multiple B- and T-cell epitopes derived from the conserved regions of two vaccine candidate antigens namely MSA-1 and RESA of human malarial parasite P. falciparum were studied for immunogenicity and protectivity. Both constructs elicited strong antibody and lymphocyte proliferation responses in BALB/c mice immunized with the carrier-free peptides. In an ELISA, these peptides also bound antibodies present in the sera from the P. vivax infected humans as well as from the P. yoelii infected mice. Significantly, our data showed that immunization of mice with these P. falciparum peptide could impart partial protection against P. yoelii challenge infection. Our finding that synthetic peptides representing portions of P. falciparum antigens were capable of stimulating protective immune responses against rodent malaria suggests that murine malaria model P. yoelii may provide a suitable system for primary screening of potentially protective synthetic immunogens.
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PMID:Synthetic peptides based on conserved Plasmodium falciparum antigens are immunogenic and protective against Plasmodium yoelii malaria. 768 76

We report on an analysis of the constraints of PCR typing of field Plasmodium falciparum isolates by using a few highly polymorphic markers, MSA-1, MSA-2, TRAP, and CS. We show that the reactions are specific for the P. falciparum species. The detection threshold (minimum number of parasites required to detect a visible band by ethidium bromide) differed from one marker to the other and, within one locus, from one primer combination to the other. Importantly, the various MSA-1 and MSA-2 reference alleles were amplified with the same efficiency. Amplification from reconstituted allele mixtures indicated that at certain allele ratios, the most abundant allele interfered with the amplification of the less abundant one. An analysis of nine isolates collected from patients with acute malaria in Dielmo, Senegal, during a transmission season when the inoculation rate was one infective bite every second night is presented and discussed. All samples contained more than one parasite type. A significant polymorphism was observed for the four markers. Novel TaqI restriction fragment length polymorphisms were found for the TRAP gene, and TRAP gene typing alone allowed a distinction between the various isolates. MSA-1 and MSA-2 gave multiple band patterns specific for each sample.
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PMID:PCR typing of field isolates of Plasmodium falciparum. 779 Apr 66

The extent of structural conservation of the Plasmodium falciparum sporozoite surface protein gene, STARP, recently characterized in the T9/96 clone, has been analyzed using the polymerase chain reaction. Results from Ivory Coast and Thai clones, field isolates originating from Brazil and Kenya and laboratory-maintained strains strongly suggest that this gene has a highly conserved structure throughout this species. This structure includes a complex repetitive central domain consisting of a mosaic region followed by tandem 45-amino acid-encoding (Rp45) and 10-amino acid-encoding (Rp10) repeat regions. Limited size variation in this domain appeared to result from highly localized duplication events in the Rp45 and Rp10 regions. No size variation was observed in the 5' and 3' coding non-repetitive regions, but minor size polymorphism was found in the single intron at the 5' end of the gene. No evidence was found of distinct families of polymorphic types, as has been observed with the blood-stage MSA-1, MSA-2 and S-antigens. The sequence of the STARP homologue in the phylogenetically close chimpanzee parasite, Plasmodium reichenowi, has also been elucidated and reveals high sequence conservation, although interesting differences were detected in the composition of the Rp10 region, known in P. falciparum to contain B- and T-cell epitopes. Finally, DNA hybridization reveals the presence in rodent malaria species of sequences containing homology to the STARP non-repetitive (though not the repetitive) regions, which would suggest that a similar, conserved gene may exist in these species.
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PMID:Conservation of the Plasmodium falciparum sporozoite surface protein gene, STARP, in field isolates and distinct species of Plasmodium. 787 Jan 30


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