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)

Recently, we found that a recombinant protein based on the 19 kDa C-terminal region of the Plasmodium vivax Merozoite Surface Protein 1 (PvMSP1(19)) was recognized by a large proportion of individuals naturally infected. The present study was designed to determine the prevalence of antibody to PvMSP1(19) in individuals from the village of Cotijuba, northern Brazil, where only P. vivax transmission occurs. Immuno-epidemiological studies on the prevalence of antibody to the C-terminus of PvMSP1 are of particular importance as this region of MSP1 is being intensively studied as a prime candidate for development of a vaccine against malaria. We evaluated the antibody response to PvMSP1(19), and compared it to the N-terminal region of PvMSP1 and to blood stage antigens. The total frequencies of individuals with IgG to blood stages, PvMSP1(19) or the N-terminal region of PvMSP1 were 76.6, 42.3 and 29.8%, respectively. The frequency of responders to PvMSP1(19) did not increase with age. However, the frequency of responders to this recombinant protein was significantly higher (77.4%) in individuals with a recent ( < 6 months) history of malaria, when compared to subjects whose last malaria attack occurred more than 6 months before (43.9%), or to individuals without a past history of symptomatic malaria (6.25%). These results confirm earlier studies by demonstrating that the PvMSP1(19) is highly immunogenic in individuals recently exposed to P. vivax malaria.
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PMID:Antibody response to the N and C-terminal regions of the Plasmodium vivax Merozoite Surface Protein 1 in individuals living in an area of exclusive transmission of P. vivax malaria in the north of Brazil. 992 57

This study reports on T-cell proliferative responses to the 19-kDa C-terminal domain of the Plasmodium falciparum merozoite surface protein (MSP1(19)). Three different recombinant proteins were used: an Escherichia coli product expressing the first EGF-like domain and Saccharomyces cerevisiae and baculovirus/insect-cell-produced proteins containing both EGF-like domains, the latter protein being produced with or without N-glycosylation. Cell donors were P. falciparum-immune adults with no recent history of clinical malaria and recruited from three Senegalese settings with different epidemiological parasite transmission. Each mononuclear-blood-cell preparation was stimulated with a range of concentrations of the three proteins. Most subjects' mononuclear cells were reactive to at least one protein, but significant differences in lymphoproliferation were seen between the settings and within individual cultures depending on the protein source and concentration. Importantly, lymphoproliferation indices correlated inversely with the intensity of P. falciparum malaria transmission. When purified T lymphocytes were cultured in the presence of MSP1(19) plus autologous monocytes, B lymphocytes or a proposed CD1+ dendritic-cell population as costimulatory cells, significant differences were observed depending on the individual's previous exposure to parasites. This study shows that the stimulation of lymphocyte proliferation in vitro with MSP1(19) depends on several factors, including epidemiological conditions and protein preparations.
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PMID:Different Plasmodium falciparum recombinant MSP1(19) antigens differ in their capacities to stimulate in vitro peripheral blood T lymphocytes in individuals from various endemic areas. 1021 71

Malaria, a disease responsible for immense human suffering, is caused by infection with Plasmodium spp. parasites, which have a very complex life cycle - antigenically unique stages infect different tissues of the body. This review details recent developments in our understanding of immunity both to pre-erythrocytic stage antigens and to erythrocytic stage antigens. The former is largely mediated via CD8(+) T cells and involves IFN-gamma, nitric oxide, IL-12 and natural killer cells; the latter varies (in different hosts and with different parasites) but is largely mediated by antibody, helper T cells, nitric oxide and gammadelta T cells. The recent progress towards clinical trials of vaccine candidates against both the pre-erythrocytic stage and erythrocytic stage is also summarized, in particular the use of heterologous prime/boost strategies for the former and the use of MSP1 as a candidate vaccine for the latter.
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PMID:Immune effector mechanisms in malaria. 1044 41

Two phase I vaccine trials were conducted to test the immunogenicity and safety of a vaccine containing three recombinant malaria antigens from the asexual stage of Plasmodium falciparum. The three antigens are a fragment of MSP1 (190LCS.T3); MSP2 and a portion of RESA and were formulated in Montanide ISA720 adjuvant. These trials investigated the dose response of each antigen for eliciting both antibody and T-cell responses and the immunogenicity of a mixture of the antigens compared with the antigens injected separately. All three antigens elicited both antibody and T-cell responses. Strong T-cell responses were observed with 190LCS.T3 and RESA with stimulation indices exceeding 100 for peripheral blood leucocytes in some individuals. The antibody responses were generally weak. The human antibody responses observed with MSP2 in Montanide ISA720 were not significantly different from those obtained in an earlier trial which used MSP2 with alum as the adjuvant. No antigenic competition was observed: volunteers receiving a mixture of antigens had similar responses to those receiving the three antigens at separate sites. Tenderness and pain at the injection site were common over the first few days following immunization. In some volunteers, especially those receiving the highest doses tested, there was a delayed reaction at the injection site with pain and swelling occurring approximately 10 days after injection.
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PMID:Human phase I vaccine trials of 3 recombinant asexual stage malaria antigens with Montanide ISA720 adjuvant. 1046 51

A Phase I safety and immunogenicity study with a three-component blood-stage malaria vaccine was conducted in adult male subjects living in an endemic area of Papua New Guinea. The preparations were recombinant proteins which corresponded to parts of the two merozoite surface proteins of Plasmodium falciparum (MSP1 and 2), and of the ring-infected erythrocyte surface antigen (RESA). The three proteins were emulsified with the adjuvant Montanide ISA720. Ten subjects were injected twice (four weeks apart) with the vaccine formulation and two with the adjuvant alone. Mild pain at the site of injection was reported by about half of the subjects but no systemic reaction related to the formulation occurred. There was a sharp rise in geometric mean stimulation index after the second dose compared to baseline for MSP1 and RESA, while the rise was small for MSP2. Geometric mean antibody titres increased for MSP1 during the study, whereas they hardly changed for MSP2 and RESA. The vaccine formulation was safe when used in an already immune population. The vaccine induced good cellular responses, especially for MSP1 and RESA. Boosting of humoral responses was weak, probably because of high baseline antibody levels.
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PMID:Safety and immunogenicity of a three-component blood-stage malaria vaccine in adults living in an endemic area of Papua New Guinea. 1077 84

To date, a high degree of polymorphism has been demonstrated at both the MSP1 and MSP2 loci in parasites from areas of stable malaria transmission. As a consequence, in such areas it is rare to find parasites of the same 2-locus genotype in more than 1 subject. We have studied MSP1 and MSP2 diversity in parasites collected from subjects with both symptomatic (n = 86) and asymptomatic (34) malaria living on the island of Santo, Vanuatu, an area of stable malaria transmission. Polymorphism at the MSP1 and MSP2 loci was considerably less than previously reported: only 5 MSP1 and 5 MSP2 alleles were detected and these showed no size variation within alleles. Santo is unique amongst the areas studied so far in that it is a small island at the limit of the malaria belt in the South Pacific. Thus, the evolution of the parasite population may have been affected by the small size and isolation of this island population. Moreover, limited parasite diversity may explain the unusually mild nature of Plasmodium falciparum disease on Santo. Islands have fascinated biologists for centuries and fuelled the advancement of evolutionary theory, since they are natural laboratories for the study of evolution. The simplicity of the Vanuatu P. falciparum population may facilitate the use and interpretation of sequence level analyses to address the mechanisms by which genetic diversity is generated and maintained in natural populations.
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PMID:Genetic restriction of Plasmodium falciparum in an area of stable transmission: an example of island evolution? 1081 Dec 74

Sequence of MSP1-31 of Plasmodium falciparum was constructed into eukaryotic expression vector pTRE, which could be repressed by tetracycline (Tc) and resulted in recombinant plasmid pTRE-31. The plasmid was injected into the quadriceps muscle of BALB/c mice with Tc responsive plasmid pTet-off to measure specific antibodies. The MSP1-31 prokaryotic expressed protein was used as antigen in ELISA. Results showed that mice orally administered by Tc had a seroconversion rate of 7.1% (1/14) 4 weeks after injection, whereas the control mice had a seroconversion rate of 100% and the titers of antibody were raised continusly within 12 weeks. The study suggested that the recombinant plasmids pTRE-31/pTet-off could efficiently induce humoral response against MSP1-31 of malaria. Moreover this immune response was controlled by Tc and was reversible after withdrawal of Tc dilivery. The induction of antibody by removing Tc at the fourth week after injection indicated that DNA vaccine could remain in mice and capable of expressing antigen for at least 4 weeks.
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PMID:[Immunization of mice with plasmid DNA against malaria and regulation of antigen expression by tetracycline-controlled promoter]. 1088 68

We report three cases of congenital malaria involving two malarial immune mothers living in Spain. Diagnostic PCR and Genotyping PCR for merozoite surface proteins 1 and 2 were essential to show that mothers and new-borns had different Plasmodium population parasites at the moment of the delivery, and that the infection was acquired earlier in gestation by transplacental transmission. In the first case the Plasmodium species founded in both, mother and child were different. Malaria in the twins showed a mixed infection (P. falciparum plus P. malariae) while the mother presented a P. falciparum infection. These facts were confirmed studying the polymorphisms for MSP1 and MSP2. Blood samples of the newborns were analyzed an half hour after delivery excluding the possibility of re-infection by mosquito bite and indicating a vertical transmission during pregnancy.
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PMID:The potential utility of the Semi-Nested Multiplex PCR technique for the diagnosis and investigation of congenital malaria. 1114 49

In this study we have investigated the antibody and CD4 T-cell responses to the well-characterized malaria vaccine candidate MSP-1 during the course of a primary Plasmodium chabaudi chabaudi (AS) infection. Specific antibody responses can be detected within the first week of infection, and CD4 T cells can be detected after 3 weeks of infection. The magnitude of the CD4 T-cell response elicited during a primary infection depended upon the region of MSP-1. In general, the highest precursor frequencies were obtained when a recombinant MSP-1 fragment corresponding to amino acids 900 to 1507 was used as the antigen in vitro. By contrast, proliferative and cytokine responses against amino acids 1508 to 1766 containing the C-terminal 21-kDa region of the molecule were low. The characteristic interleukin 4 (IL-4) switch that occurs in the CD4 T-cell population after an acute blood stage P. c. chabaudi infection was only consistently observed in the response to the amino acid 900 to 1507 MSP1 fragment. A lower frequency of IL-4-producing cells was seen in response to other regions. Although the magnitudes of the immunoglobulin G antibody responses to the different regions of MSP-1 were similar, the isotype composition of each response was distinct, and there was no obvious relationship with the type of T helper cells generated. Interestingly, a relatively high antibody response to the C-terminal region of MSP-1 was observed, suggesting that T-cell epitopes outside of this region may provide the necessary cognate help for specific antibody production.
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PMID:Different regions of the malaria merozoite surface protein 1 of Plasmodium chabaudi elicit distinct T-cell and antibody isotype responses. 1125 80

By motif searching of the unfinished sequences in the Malaria Genome Sequencing Project databases we have identified a novel EGF-like domain-containing protein of Plasmodium falciparum. The sequence lies within a single open reading frame of 1791 bp and is predicted to encode a polypeptide of 597 amino acids. There are hydrophobic regions at the extreme N- and C-termini, which could represent secretory signal peptide and GPI attachment sites, respectively. Similar to MSP1, there are two EGF-like domains located near the C-terminus. RT-PCR analysis of the novel gene shows that it is transcribed in asexual stages of the malaria parasite. We have expressed portions of the protein as recombinant GST fusions in Escherichia coli and raised antisera in rabbits. Antibodies to the EGF-like domains of the novel protein are highly specific and do not cross-react with the EGF-like domains of MSP1, MSP4 or MSP5 expressed as GST fusion proteins. Antiserum raised to the most C-terminal region of the protein reacts with four bands of 98, 50, 25 and 19 kDa in P. falciparum parasite lysates whereas antisera to the N-terminal fusion proteins recognise the 98 and 50 kDa bands, suggesting that the novel protein may undergo processing in a similar way to MSP1. Immunoblot analysis of stage-specific parasite samples reveals that the protein is present throughout the parasite asexual life cycle and in isolated merozoites, with the smaller fragments present in ring stage parasites. The protein partitions in the detergent-enriched phase after Triton X-114 fractionation and is localized to the surfaces of trophozoites, schizonts and free merozoites by indirect immunofluorescence. Antisera to the C-terminus stain the surface of rings, whereas antisera to the N-terminus do not, suggesting that a fragment of the protein is carried into the developing ring stage parasite. Based on the accepted nomenclature in the field we designate this protein MSP8. We have shown that the MSP8 fusion proteins are in a conformation that can be recognised by human immune sera and that there is very limited diversity in the MSP8 gene sequences from various P. falciparum laboratory isolates. MSP8 shows significant similarity to the recently reported sequence of the protective P. yoelii merozoite surface protein pypAg-2 [Burns JM, Belk CC, Dunn PD. Infect Immun 2000;68:6189-95.] suggesting that the two proteins are homologues. Taken together, these findings suggest that MSP8/pypAg-2 may play an important role in the process of red cell invasion and is a potential malaria vaccine candidate.
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PMID:Merozoite surface protein 8 of Plasmodium falciparum contains two epidermal growth factor-like domains. 1137 1


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