| adjuvanticity and protective immunity of plasmodium yoelii nigeriensis blood-stage soluble antigens encapsulated in fusogenic liposome. | in our previous studies we established fusogenic properties of lipids isolated from edible yeast saccharomyces cerevisiae (s. cerevisiae). we demonstrated that liposomes prepared from s. cerevisiae membrane lipid (saccharosome) can deliver encapsulated antigen into cytosol of the antigen presenting cells and elicit antigen specific cell mediated as well as humoral immune responses. in this study, we evaluated immunological behavior of saccharosome encapsulated cytosolic proteins (sag) of plasmod ... | 2009 | 18996429 |
| novel bis- and tris-1,2,4-trioxanes: synthesis and antimalarial activity against multidrug-resistant plasmodium yoelii in swiss mice. | a new series of bis-1,2,4-trioxanes 12a-h, 13a-h, and 14a-h and tris-1,2,4-trioxanes 12i-14i were prepared and evaluated against multidrug-resistant plasmodium yoelii in swiss mice by oral route. cyclopentane-based bis-trioxanes 12a, 12b, 12f-h and cyclohexane-based bis-trioxanes 13a, 13f, and 13g showed promising activity. all the tris-1,2,4-trioxanes were found to be inactive. bis-trioxane 12a, the most active compound of the series, provided 100% and 80% protection to infected mice at 48 and ... | 2008 | 19006381 |
| recombinant peptide replicates immunogenicity of synthetic linear peptide chimera for use as pre-erythrocytic stage malaria vaccine. | synthetic linear peptide chimeras (lpcs(cys+)) show promise as delivery platforms for malaria subunit vaccines. maximal immune response to lpcs(cys+) in rodent malaria models depends upon formation of cross-linkages to generate homopolymers, presenting challenges for vaccine production. to replicate the immunogenicity of lpcs(cys+) using a recombinant approach, we designed a recombinant lpc (rlpc) based on plasmodium yoelii circumsporozoite protein-specific sequences of 208 amino acids consistin ... | 2009 | 19015042 |
| effect of plasmodium yoelii exposure on vaccination with the 19-kilodalton carboxyl terminus of merozoite surface protein 1 and vice versa and implications for the application of a human malaria vaccine. | it is well known that exposure to one antigen can modulate the immune responses that develop following exposure to closely related antigens. it is also known that the composition of the repertoire can be skewed to favor epitopes shared between a current infection and a preceding one, a phenomenon referred to as "original antigenic sin." it was of interest, therefore, to investigate the antibody response that develops following exposure to the malaria vaccine candidate homologue plasmodium yoelii ... | 2009 | 19015251 |
| hiv protease inhibitors inhibit the development of preerythrocytic-stage plasmodium parasites. | recent studies have demonstrated that human immunodeficiency virus (hiv) protease inhibitors (pis) exert inhibitory effects on erythrocytic stages of the human-malaria parasite plasmodium falciparum in vitro and on erythrocytic stages of the rodent-malaria parasite plasmodium chabaudi in vivo. although it remains unclear how hiv pis inhibit the parasite, the effect seen on parasite development in the erythrocytic stages is potent. the effect on preerythrocytic stages has not yet been investigate ... | 2009 | 19032102 |
| vaccination with live plasmodium yoelii blood stage parasites under chloroquine cover induces cross-stage immunity against malaria liver stage. | immunity to malaria has long been thought to be stage-specific. in this study we show that immunization of balb/c mice with live erythrocytes infected with nonlethal strains of plasmodium yoelii under curative chloroquine cover conferred protection not only against challenge by blood stage parasites but also against sporozoite challenge. this cross-stage protection was dose-dependent and long lasting. cd4(+) and cd8(+) t cells inhibited malaria liver but not blood stage. their effect was mediate ... | 2008 | 19050274 |
| mitochondrial dehydrogenases in the aerobic respiratory chain of the rodent malaria parasite plasmodium yoelii yoelii. | in the intraerythrocytic stages of malaria parasites, mitochondria lack obvious cristae and are assumed to derive energy through glycolysis. for understanding of parasite energy metabolism in mammalian hosts, we isolated rodent malaria mitochondria from plasmodium yoelii yoelii grown in mice. as potential targets for antiplasmodial agents, we characterized two respiratory dehydrogenases, succinate:ubiquinone reductase (complex ii) and alternative nadh dehydrogenase (ndh-ii), which is absent in m ... | 2009 | 19060309 |
| postnatal development and resistance to plasmodium yoelii infection of mice prenatally exposed to triphenyltin hydroxide. | in this study, we evaluated the effects of prenatal exposure to triphenyltin hydroxide (tpth) on the postnatal development of swiss webster mice. females were treated by gavage (0, 7.5 15 and 30 mg tpth/kg/day) on days 6-17 of gestation. after birth, the progeny was examined for deaths, body weight gain and appearance of developmental landmarks. on postnatal day 50, one male and one female of each litter were inoculated with plasmodium yoelii and the time-course of infection was monitored. tpth ... | 2009 | 19065682 |
| type ii fatty acid synthesis is essential only for malaria parasite late liver stage development. | intracellular malaria parasites require lipids for growth and replication. they possess a prokaryotic type ii fatty acid synthesis (fas ii) pathway that localizes to the apicoplast plastid organelle and is assumed to be necessary for pathogenic blood stage replication. however, the importance of fas ii throughout the complex parasite life cycle remains unknown. we show in a rodent malaria model that fas ii enzymes localize to the sporozoite and liver stage apicoplast. targeted deletion of fabb/f ... | 2009 | 19068099 |
| the effects of radiation on the safety and protective efficacy of an attenuated plasmodium yoelii sporozoite malaria vaccine. | we are developing a radiation attenuated plasmodium falciparum sporozoite (pfspz) malaria vaccine. an important step was to determine the minimum dose of irradiation required to adequately attenuate each sporozoite. this was studied in the plasmodium yoelii rodent model system. exposure to 100 gy completely attenuated p. yoelii sporozoites (pyspz). next we demonstrated that immunization of mice intravenously with 3 doses of 750 pyspz that had received 200 gy, double the radiation dose required f ... | 2009 | 19071177 |
| identification of new inhibitors for alternative nadh dehydrogenase (ndh-ii). | in bacterial membranes and plant, fungus and protist mitochondria, nadh dehydrogenase (ndh-ii) serves as an alternative nadh : quinone reductase, a non-proton-pumping single-subunit enzyme bound to the membrane surface. because ndh-ii is absent in mammalian mitochondria, it is a promising target for new antibiotics. however, inhibitors for ndh-ii are rare and unspecific. taking advantage of the simple organization of the respiratory chain in gluconobacter oxydans, we carried out screening of nat ... | 2009 | 19076229 |
| a plasmodium yoelii soluble factor inhibits the phenotypic maturation of dendritic cells. | infection with the protozoan parasite plasmodium is the cause of malaria. plasmodium infects host erythrocytes causing the pathology of the disease. plasmodium-infected erythrocytes can modulate the maturation of dendritic cells (dcs) and alter their capacity to activate t cells. | 2008 | 19077314 |
| plasmodium yoelii: assessment of production and role of nitric oxide during the early stages of infection in susceptible and resistant mice. | there is conflicting evidence regarding the role of nitric oxide (no) in the process of resistance against blood-stage malaria parasites. in this study, we used two strains of mice infected with plasmodium yoelii 17xl in order to assess the no production profile and its possible role during the early stage of malaria infection. we found a greater elevation of no production associated with a sharp increase in the levels of ifn-gamma in infected dba/2 mice, compared with infected balb/c mice. this ... | 2009 | 19109953 |
| rapid changes in transcription profiles of the plasmodium yoelii yir multigene family in clonal populations: lack of epigenetic memory? | the pir multigene family, found in the genomes of plasmodium vivax, p. knowlesi and the rodent malaria species, encode variant antigens that could be targets of the immune response. individual parasites of the rodent malaria plasmodium yoelii, selected by micromanipulation, transcribe only 1 to 3 different pir (yir) suggesting tight transcriptional control at the level of individual cells. using microarray and quantitative rt-pcr, we show that despite this very restricted transcription in a sing ... | 2009 | 19173007 |
| the shiitake mushroom-derived immuno-stimulant lentinan protects against murine malaria blood-stage infection by evoking adaptive immune-responses. | lentinan, a (1-3)-beta glucan from lentinus edodes, is an effective immunostimulatory drug. we tested the effects of lentinan during blood-stage infection by plasmodium yoelii 17xl (p.y17xl). pre-treatment of mice with lentinan significantly decreased the parasitemia and increased their survival after infection. enhanced il-12, ifn-gamma and no production induced by lentinan in spleen cells of infected mice revealed that the th1 immune response was stimulated against malaria infection. in vitro ... | 2009 | 19189863 |
| polymeric linear peptide chimeric vaccine-induced antimalaria immunity is associated with enhanced in vitro antigen loading. | immunization of mice with plasmodium berghei or plasmodium yoelii synthetic linear peptide chimeras (lpcs) based on the circumsporozoite protein protects against experimental challenge with viable sporozoites. the immunogenicity of lpcs is significantly enhanced by spontaneous polymerization. to better understand the antigenic properties of polymeric antimalarial peptides, we studied the immune responses elicited in mice immunized with a polymer or a monomer of a linear peptide construct specifi ... | 2009 | 19237530 |
| plasmodium: mammalian codon optimization of malaria plasmid dna vaccines enhances antibody responses but not t cell responses nor protective immunity. | we have evaluated the effect of mammalian codon optimization on the immunogenicity and protective efficacy of plasmid dna vaccines encoding pre-erythrocytic stage plasmodium falciparum and plasmodium yoelii antigens in mice. codon optimization significantly enhanced in vitro expression and in vivo antibody responses for p. falciparum circumsporozoite protein (pfcsp) and p. yoelii hepatocyte erythrocyte protein 17 kda (pyhep17) but not for p. yoelii circumsporozoite protein (pycsp). unexpectedly, ... | 2009 | 19249301 |
| plasmodium chabaudi: expression of active recombinant chabaupain-1 and localization studies in anopheles sp. | plasmodium cysteine proteases have been shown to be immunogenic and are being used as malaria potential serodiagnostic markers and vaccine targets. genes encoding two plasmodium chabaudi cysteine proteases chabaupain-1 (cp-1) and chabaupain-2 (cp-2) were identified and further expressed in escherichia coli. solubilisation of recombinant cp-1 and cp-2 was achieved by decreasing the temperature of induction. anopheles gambiae tissues infected with plasmodium were analyzed by western blotting using ... | 2009 | 19292986 |
| synthesis of novel thiourea, thiazolidinedione and thioparabanic acid derivatives of 4-aminoquinoline as potent antimalarials. | in search of new 4-aminoquinolines which are not recognized by cqr mechanism, thiourea, thiazolidinedione and thioparabanic acid derivatives of 4-aminoquinoline were synthesized and screened for their antimalarial activities. thiourea derivative 3 found to be the most active against cq sensitive strain 3d7 of plasmodium falciparum in an in vitro model with an ic(50) of 6.07ng/ml and also showed an in vivo suppression of 99.27% on day 4 against cq resistant strain n-67 of plasmodium yoelii. | 2009 | 19339178 |
| single amino acid substitution in plasmodium yoelii erythrocyte ligand determines its localization and controls parasite virulence. | the major virulence determinant of the rodent malaria parasite, plasmodium yoelii, has remained unresolved since the discovery of the lethal line in the 1970s. because virulence in this parasite correlates with the ability to invade different types of erythrocytes, we evaluated the potential role of the parasite erythrocyte binding ligand, pyebl. we found 1 amino acid substitution in a domain responsible for intracellular trafficking between the lethal and nonlethal parasite lines and, furthermo ... | 2009 | 19346470 |
| gene encoding erythrocyte binding ligand linked to blood stage multiplication rate phenotype in plasmodium yoelii yoelii. | variation in the multiplication rate of blood stage malaria parasites is often positively correlated with the severity of the disease they cause. the rodent malaria parasite plasmodium yoelii yoelii has strains with marked differences in multiplication rate and pathogenicity in the blood. we have used genetic analysis by linkage group selection (lgs) to identify genes that determine differences in multiplication rate. genetic crosses were generated between genetically unrelated, fast- (17xym) an ... | 2009 | 19359470 |
| plasmodium yoelii: adverse outcome of non-lethal p. yoelii malaria during co-infection with schistosoma mansoni in balb/c mouse model. | plasmodium yoelii and schistosoma mansoni co-infections were studied in female balb/c mice aged 4-6 weeks to determine the effect of time and stage of concomitant infections on malaria disease outcome. patent s. mansoni infection in balb/c mice increased malaria peak parasitemia and caused death from an otherwise non-lethal, self-resolving p. yoelii malaria infection. exacerbation of malaria parasitemia occurred during both pre-patent and patent s. mansoni infection resulting in a delay of 4-8 d ... | 2009 | 19366621 |
| rodent malaria-resistant strains of the mosquito, anopheles gambiae, have slower population growth than -susceptible strains. | trade-offs between anti-parasite defence mechanisms and other life history traits limit the evolution of host resistance to parasites and have important implications for understanding diseases such as malaria. mosquitoes have not evolved complete resistance to malaria parasites and one hypothesis is that anti-malaria defence mechanisms are costly. | 2009 | 19379508 |
| thermal behaviour of anopheles stephensi in response to infection with malaria and fungal entomopathogens. | temperature is a critical determinant of the development of malaria parasites in mosquitoes, and hence the geographic distribution of malaria risk, but little is known about the thermal preferences of anopheles. a number of other insects modify their thermal behaviour in response to infection. these alterations can be beneficial for the insect or for the infectious agent. given current interest in developing fungal biopesticides for control of mosquitoes, anopheles stephensi were examined to tes ... | 2009 | 19379519 |
| hundreds of microsatellites for genotyping plasmodium yoelii parasites. | genetic crosses have been employed to study various traits of rodent malaria parasites and to locate loci that contribute to drug resistance, immune protection, and disease virulence. compared with human malaria parasites, genetic crossing of rodent malaria parasites is more easily performed; however, genotyping methods using microsatellites (mss) or large-scale single nucleotide polymorphisms (snps) that have been widely used in typing plasmodium falciparum are not available for rodent malaria ... | 2009 | 19450732 |
| [inhibition of cpg oligodeoxynucleotide on the development of pre-erythrocytic stage of plasmodium]. | to study the role of cytidine-phosphate-guanosine oligodeoxynucleotide (cpg odn) on the development of plasmodium liver stage. | 2009 | 19459490 |
| human t cell recognition of the blood stage antigen plasmodium hypoxanthine guanine xanthine phosphoribosyl transferase (hgxprt) in acute malaria. | the plasmodium purine salvage enzyme, hypoxanthine guanine xanthine phosphoribosyl transferase (hgxprt) can protect mice against plasmodium yoelii prbc challenge in a t cell-dependent manner and has, therefore, been proposed as a novel vaccine candidate. it is not known whether natural exposure to plasmodium falciparum stimulates hgxprt t cell reactivity in humans. | 2009 | 19500406 |
| an early burst of ifn-gamma induced by the pre-erythrocytic stage favours plasmodium yoelii parasitaemia in b6 mice. | in murine models of malaria, an early proinflammatory response has been associated with the resolution of blood-stage infection. to dissect the protective immune mechanism that allow the control of parasitaemia, the early immune response of c57bl/6 mice induced during a non-lethal plasmodial infection was analysed. | 2009 | 19508725 |
| methotrexate and aminopterin lack in vivo antimalarial activity against murine malaria species. | the antifolate anticancer drug methotrexate (mtx) has potent activity against plasmodium falciparum in vitro. experience of its use in the treatment of rheumatoid arthritis indicates that it could be safe and efficacious for treating malaria. we sought to establish a murine malaria model to study the mechanism of action and resistance of mtx and its analogue aminopterin (amp). we used plasmodium berghei, plasmodium yoelii yoelii, plasmodium chabaudi and plasmodium vinckei. none of these species ... | 2009 | 19527714 |
| involvement of prophenoloxidases in the suppression of plasmodium yoelii development by anopheles dirus. | anopheles dirus is refractory to a rodent malaria parasite, plasmodium yoelii, and melanized oocysts are manifested in infected mosquitoes. prophenoloxidase (ppo) is a zymogen whose active form mediates melanotic encapsulation of invading pathogens in mosquitoes. in this study, we cloned cdna fragments of four an. dirus ppos, that are orthologs of anopheles gambiae ppo2, ppo4, ppo5 and ppo6. adppo4 expression in hemocytes was induced in response to p. yoelii infection. rna interference using dou ... | 2009 | 19540233 |
| effects of cd4(+)cd25(+)foxp3(+)regulatory t cells on early plasmodium yoelii 17xl infection in balb/c mice. | the outcome of plasmodium yoelii 17xl-infected balb/c and dba/2 mice, ranging from death to spontaneous cure, respectively, depends largely on the establishment of effective pro-inflammatory type 1 responses during the early stages of infection and associates with cd4(+)cd25(+)foxp3(+)regulatory t cells (tregs). here, effects of tregs were analysed on early p. yoelii 17xl infection in balb/c and dba/2 mice. in vivo depletion of tregs significantly reversed the inhibited establishment of effectiv ... | 2009 | 19573259 |
| search for new pharmacophores for antimalarial activity. part iii: synthesis and bioevaluation of new 6-thioureido-4-anilinoquinazolines. | syntheses and in vitro antimalarial evaluation of 42 new thioureidoquinazolines have been carried out. several analogs showed promising antimalarial effect in the in vitro investigation against chloroquine-sensitive 3d7 strain of plasmodium falciparum whereas one of the compounds shows 50% curative effect in the mouse model at an oral dose of 100mg/kg x 4 days against multidrug resistant plasmodium yoelii nigeriensis. | 2009 | 19586687 |
| inhibitory antibodies specific for the 19-kilodalton fragment of merozoite surface protein 1 do not correlate with delayed appearance of infection with plasmodium falciparum in semi-immune individuals in vietnam. | inhibitory antibodies specific for the 19-kda fragment of merozoite surface protein 1 (msp1(19)) are a significant component of inhibitory responses in individuals immune to malaria. nevertheless, conflicting results have been obtained in determining whether this antibody specificity correlates with protection in residents of areas where malaria is endemic. in this study, we examined sera collected from a population of semi-immune individuals living in an area of vietnam with meso-endemicity dur ... | 2009 | 19620342 |
| inhibitory role of toll-like receptors agonists in plasmodium yoelii liver stage development. | it is well known that innate immune plays an important role in controlling the development of plasmodium liver stage. however, little is known about the role of toll-like receptors (tlr) signalling in the pre-erythrocytic immunity against plasmodium. here, we found that pre-treatment with individual tlr agonist pam3csk4 (tlr2), poly(i:c) (tlr3), lps (tlr4) and cpg (tlr9) could decrease significantly the liver malaria parasite load in mice for 58%, 63%, 75% and 88% respectively. moreover, no para ... | 2009 | 19646211 |
| synthesis of oxalamide and triazine derivatives as a novel class of hybrid 4-aminoquinoline with potent antiplasmodial activity. | frequency of malaria and its resistance to chemotherapeutic options are emerging rapidly. to counter this problem, a series of 4-aminoquinolines having oxalamide and triazine functionalities in the side chain were synthesized and screened for their antimalarial activities. triazine derivative 48 found to be the most active against cq sensitive strain 3d7 of plasmodium falciparum in an in vitro assay with an ic(50) of 5.23 ng/ml and oxalamide derivative 13 showed an in vivo suppression of 70.45% ... | 2009 | 19665899 |
| generation, annotation, and analysis of ests from midgut tissue of adult female anopheles stephensi mosquitoes. | malaria is a tropical disease caused by protozoan parasite, plasmodium, which is transmitted to humans by various species of female anopheline mosquitoes. anopheles stephensi is one such major malaria vector in urban parts of the indian subcontinent. unlike anopheles gambiae, an african malaria vector, transcriptome of a. stephensi midgut tissue is less explored. we have therefore carried out generation, annotation, and analysis of expressed sequence tags from sugar-fed and plasmodium yoelii inf ... | 2009 | 19695102 |
| concurrent infection with heligmosomoides polygyrus suppresses anti-plasmodium yoelii protection partially by induction of cd4(+)cd25(+)foxp3(+) treg in mice. | malaria and intestinal nematode infection are widespread and co-infection frequently occurs. we investigated whether co-infected intestinal nematodes modulate immunity against co-existing malaria parasites. infection of c57bl/6 mice with plasmodium yoelii 17xnl (py) was transient and self-limiting, but preceding infection with heligmosomoides polygyrus (hp), a mouse intestinal nematode, exacerbated malaria resulting in higher parasite burdens and poor survival of the mice. co-infection with hp l ... | 2009 | 19728313 |
| malaria ookinete surface protein-based vaccination via the intranasal route completely blocks parasite transmission in both passive and active vaccination regimens in a rodent model of malaria infection. | malaria vaccines based on ookinete surface proteins (osps) of the malaria parasites block oocyst development in feeding mosquitoes and hence disrupt the parasite life cycle and prevent the disease from being transmitted to other individuals. to investigate whether a noninvasive mucosal vaccination regimen effectively blocks parasite transmission in vivo, plasmodium yoelii pys25, a homolog of the pfs25 and pvs25 osps of plasmodium falciparum and plasmodium vivax, respectively, was intranasally (i ... | 2009 | 19752035 |
| the ig domain protein cd9p-1 down-regulates cd81 ability to support plasmodium yoelii infection. | invasion of hepatocytes by plasmodium sporozoites is a prerequisite for establishment of a malaria natural infection. the molecular mechanisms underlying sporozoite invasion are largely unknown. we have previously reported that cd81 is required on hepatocytes for infection by plasmodium falciparum and plasmodium yoelii sporozoites. cd81 belongs to the tetraspanin superfamily of transmembrane proteins. by interacting with each other and with other transmembrane proteins, tetraspanins may play a r ... | 2009 | 19762465 |
| production and characterization of an orally immunogenic plasmodium antigen in plants using a virus-based expression system. | increasing numbers of plant-made vaccines and pharmaceuticals are entering the late stage of product development and commercialization. despite the theoretical benefits of such production, expression of parasite antigens in plants, particularly those from plasmodium, the causative parasites for malaria, have achieved only limited success. we have previously shown that stable transformation of tobacco plants with a plant-codon optimized form of the plasmodium yoelii merozoite surface protein 4/5 ... | 2009 | 19781007 |
| comparative study between non lethal and lethal strains of plasmodium yoelii with reference to its immunological aspect. | innate immunity has an important role in the protection against malaria. to clarify the effect on non lethal and lethal strain of plasmodium yoelii, comparison between two groups of c57bl/6 mice infected with 10(4) parasitized rbcs was performed. liver and spleen mononuclear cells were isolated and analyzed by flow cytometry. the parasite appeared in blood on day 3 in both strains, with non lethal infection parasitemia reached a peak of 60% on day 14 and mice completely recovered, while in letha ... | 2009 | 19795764 |
| noninvasive real-time monitoring of liver-stage development of bioluminescent plasmodium parasites. | the morbidity and mortality associated with malaria are heightened because of the spread of drug-resistant parasites and the lack of an effective vaccine. plasmodium liver stages are the targets of new chemotherapeutics and vaccines, but there are limited tools available to study this stage in vivo. | 2009 | 19811100 |
| genetically attenuated parasite vaccines induce contact-dependent cd8+ t cell killing of plasmodium yoelii liver stage-infected hepatocytes. | the production of ifn-gamma by cd8(+) t cells is an important hallmark of protective immunity induced by irradiation-attenuated sporozoites against malaria. here, we demonstrate that protracted sterile protection conferred by a plasmodium yoelii genetically attenuated parasite (pygap) vaccine was completely dependent on cd8(+) t lymphocytes but only partially dependent on ifn-gamma. we used live cell imaging to document that cd8(+) ctl from pygap-immunized mice directly killed hepatocyte infecte ... | 2009 | 19812194 |
| in vivo antiparasitic activity of the thai traditional medicine plant--tinospora crispa--against plasmodium yoelii. | we investigated the in vivo antimalarial effect of crude extract of tinospora crispa, a thai traditional medicine plant. mice were inoculated with plasmodium yoelii then treated with the crude extract of tinospora crispa at doses of 20, 40 and 80 mg/kg. mice receiving the dose of 20 mg/kg died on average on day 8. mice remained alive longer when treated of the dose of 40 mg/kg or even longer under the treatment of the dose of 80 mg/kg. surprisingly and interestingly, one mouse from the group in ... | 2009 | 19842370 |
| synthesis of 9-anilinoacridine triazines as new class of hybrid antimalarial agents. | there is challenge and urgency to synthesize cost-effective chemotherapeutic agents for treatment of malaria after the widespread development of resistance to cq. in the present study, we synthesized a new series of hybrid 9-anilinoacridine triazines using the cheap chemicals 6,9-dichloro-2-methoxy acridine and cyanuric chloride. the series of new hybrid 9-anilinoacridine triazines were evaluated in vitro for their antimalarial activity against cq-sensitive 3d7 strain of plasmodium falciparum an ... | 2009 | 19879137 |
| vaxfectin enhances both antibody and in vitro t cell responses to each component of a 5-gene plasmodium falciparum plasmid dna vaccine mixture administered at low doses. | we previously reported the capacity of the cationic lipid-based formulation, vaxfectin, to enhance the immunogenicity and protective efficacy of a low dose plasmid dna vaccine against plasmodium yoelii malaria in mice. here, we have extended this finding to human plasmodium falciparum genes, evaluating the immune enhancing effect of vaxfectin formulation on a mixture, designated cslam, of five plasmid dna vaccines encoding antigens from the sporozoite (pfcsp, pfssp2/trap), intrahepatic (pflsa1), ... | 2010 | 19879998 |
| baculovirus-based nasal drop vaccine confers complete protection against malaria by natural boosting of vaccine-induced antibodies in mice. | blood-stage malaria parasites ablate memory b cells generated by vaccination in mice, resulting in diminishing natural boosting of vaccine-induced antibody responses to infection. here we show the development of a new vaccine comprising a baculovirus-based plasmodium yoelii 19-kda carboxyl terminus of merozoite surface protein 1 (pymsp1(19)) capable of circumventing the tactics of parasites in a murine model. the baculovirus-based vaccine displayed pymsp1(19) on the surface of the virus envelope ... | 2010 | 19901059 |
| erythrocyte binding ligands in malaria parasites: intracellular trafficking and parasite virulence. | the intracellular trafficking of an erythrocyte binding like (ebl) ligand has recently been shown to dramatically affect the multiplication rate and virulence of the rodent malaria parasite plasmodium yoelii yoelii. in this review, we describe the current understanding of the role of ebl and other erythrocyte binding ligands in erythrocyte invasion, and discuss the mechanisms by which they may control multiplication rates and virulence in malaria parasites. | 2010 | 19913491 |
| growth-inhibitory antibodies are not necessary for protective immunity to malaria infection. | the absence of a validated surrogate marker for the immune state has complicated the design of a subunit vaccine against asexual stages of plasmodium falciparum. in particular, it is not known whether the capacity to induce antibodies that inhibit parasite growth in vitro is an important criterion for selection of p. falciparum proteins to be assessed in human vaccine trials. we examined this issue in the plasmodium yoelii rodent malaria model using the 19-kda c-terminal fragment of merozoite su ... | 2010 | 19917716 |
| cd8+ t cell adjuvant effects of salmonella flicd flagellin in live vaccine vectors or as purified protein. | salmonella flagellin, the flagellum structural subunit, has received particular interest as a vaccine adjuvant conferring enhanced immunogenity to soluble proteins or peptides, both for activation of antibody and cellular immune responses. in the present study, we evaluated the salmonella enterica flicd flagellin as a t cell vaccine adjuvant using as model the 9-mer (syvpsaeqi) synthetic h2(d)-restricted cd8(+) t cell-specific epitope (cs(280-288)) derived from the plasmodium yoelii circumsporoz ... | 2010 | 19932669 |
| antigen fusion with c3d3 augments or inhibits humoral immunity to aav genetic vaccines in a transgene-dependent manner. | genetic fusion of tandem repeats of the complement molecule c3d has been shown to considerably enhance immune responses to genetic vaccines. we have investigated the applicability of this approach to augment humoral immune responses toward vaccines delivered by recombinant adeno-associated virus (aav) vectors. c3d(3)-fusion was found to markedly decrease antibody responses to merozoite surface protein 4/5 from plasmodium yoelii and contrasted with greater than 50-fold enhancement in responses wh ... | 2010 | 19935770 |
| structural and functional comparison of mif ortholog from plasmodium yoelii with mif from its rodent host. | host-derived macrophage migration inhibitory factor (mif) has been implicated in the pathogenesis of malaria infection, especially in malarial anemia. although two plasmodium parasite-derived mif orthologs, plasmodium falciparum mif and p. berghei mif were identified recently, the crystal structure and the precise roles of plasmodium-derived mifs, particularly in combination with the host mif, remain unknown. in this study, we identified another mif ortholog from a rodent-specific p. yoelii (pym ... | 2010 | 20004020 |
| toward the discovery of vaccine adjuvants: coupling in silico screening and in vitro analysis of antagonist binding to human and mouse ccr4 receptors. | adjuvants enhance or modify an immune response that is made to an antigen. an antagonist of the chemokine ccr4 receptor can display adjuvant-like properties by diminishing the ability of cd4+cd25+ regulatory t cells (tregs) to down-regulate immune responses. | 2009 | 20011659 |
| synthesis of new chalcone derivatives containing acridinyl moiety with potential antimalarial activity. | a series of novel chalcones bearing acridine moiety attached to the amino group in their ring a have been synthesized through noncatalyzed nucleophilic aromatic substitution reaction between various 3'-aminochalcone or 4'-aminochalcones and 9-chloroacridine. the synthesized chalcone derivatives have been characterized and screened for in vitro antimalarial activity against plasmodium falciparum nf-54. all the chalcones showed complete inhibition at concentration of 10 microg/ml and above while t ... | 2010 | 20022412 |
| synthesis and evaluation of phenylequine for antimalarial activity in vitro and in vivo. | synthesis of the potent antiplasmodial 4-aminoquinoline, phenylequine (pq), is reported for the first time. pq and the two analogues show increased efficacy in moving from the chloroquine sensitive d10 to the chloroquine resistant k1 strain in vitro. the in vivo efficacy of pq, and salts thereof, have been determined in plasmodium berghei anka and plasmodium yoelii. phenylequine hydrochloride has shown an ed(50) of 0.81 in p. yoelii (cf chloroquine ed(50)=1.31). | 2010 | 20034790 |
| a dispensable plasmodium locus for stable transgene expression. | the ribosomal small subunit locus has been used for transgene expression in the rodent malaria parasites, plasmodium berghei and plasmodium yoelii, but this strategy utilizes single crossover integration and is thus prone to reversion by plasmid excision. targeting of the ribosomal subunit locus may also have a negative effect on oocyst development in the mosquito. in p. berghei, the p230 paralog locus has been used for transgene expression. here, we show that the p. yoelii s1 locus (sporozoite ... | 2010 | 20045029 |
| [correlation of anopheles tep1 gene with melanization induced by nitroquine]. | to analyze the relationship between the tep1 gene of anopheles stephensi and melanotic encapsulation of plasmodium yoelii induced by anti-malaria drug nitroquine. | 2009 | 20066988 |
| a multifactorial mechanism in the superior antimalarial activity of alpha-c-galcer. | we have previously shown that the c-glycoside analog of alpha-galactosylceramide (alpha-galcer), alpha-c-galcer, displays a superior inhibitory activity against the liver stages of the rodent malaria parasite plasmodium yoelii than its parental glycolipid, alpha-galcer. in this study, we demonstrate that nk cells, as well as il-12, are a key contributor for the superior activity displayed by alpha-c-galcer. surprisingly, the diminished production of th2 cytokines, including il-4, by alpha-c-galc ... | 2010 | 20069056 |
| anti-peptide antibodies differentiate between plasmodial lactate dehydrogenases. | malaria lactate dehydrogenase, a glycolytic enzyme, is a malaria diagnostic target in lateral flow immunochromatographic rapid diagnostic tests. recombinant plasmodium yoelii ldh was cloned into the pet-28a vector, expressed and the expressed protein purified from a ni-nta affinity matrix. a pan-malarial ldh antibody directed against a common malaria ldh peptide (apgksdkewnrddll) and two anti-peptide antibodies, each targeting a unique plasmodium falciparum (lisdaeleaifdc) and plasmodium vivax ( ... | 2010 | 20093160 |
| genetic linkage of autologous t cell epitopes in a chimeric recombinant construct improves anti-parasite and anti-disease protective effect of a malaria vaccine candidate. | we have reported the design of polyvalent synthetic and recombinant chimeras that include promiscuous t cell epitopes as a viable delivery system for pre-erythrocytic subunit malaria vaccines. to further assess the ability of several plasmodium t cell epitopes to enhance vaccine potency, we designed a synthetic gene encoding four plasmodium yoelii merozoite surface protein 1 (pymsp1) cd4(+) promiscuous t cell epitopes fused in tandem to the homologous carboxyl terminal pymsp1(19) fragment. this ... | 2010 | 20097151 |
| both hemolytic anemia and malaria parasite-specific factors increase susceptibility to nontyphoidal salmonella enterica serovar typhimurium infection in mice. | severe pediatric malaria is an important risk factor for developing disseminated infections with nontyphoidal salmonella serotypes (nts). while recent animal studies on this subject are lacking, early work suggests that an increased risk for developing systemic nts infection during malaria is caused by hemolytic anemia, which leads to reduced macrophage microbicidal activity. here we established a model for oral salmonella enterica serotype typhimurium challenge in mice infected with plasmodium ... | 2010 | 20100860 |
| involvement of cd8+ t cells in protective immunity against murine blood-stage infection with plasmodium yoelii 17xl strain. | when developing malaria vaccines, the most crucial step is to elucidate the mechanisms involved in protective immunity against the parasites. we found that cd8(+) t cells contribute to protective immunity against infection with blood-stage parasites of plasmodium yoelii. infection of c57bl/6 mice with p. yoelii 17xl was lethal, while all mice infected with a low-virulence strain of the parasite 17xnl acquired complete resistance against re-infection with p. yoelii 17xl. however, the host mice tr ... | 2010 | 20101613 |
| plasmodium yoelii-infected a. stephensi inefficiently transmit malaria compared to intravenous route. | it was recently reported that when mosquitoes infected with p. berghei sporozoites feed on mice, they deposit approximately 100-300 sporozoites in the dermis. when we inoculate p. yoelii (py) sporozoites intravenously (iv) into balb/c mice, the 50% infectious dose (id(50)) is often less than 3 sporozoites, indicating that essentially all py sporozoites in salivary glands are infectious. thus, it should only take the bite of one infected mosquito to infect 100% of mice. in human subjects, it take ... | 2010 | 20126610 |
| cd4+cd25+foxp3+ regulatory t cells prevent the development of th1 immune response by inhibition of dendritic cell function during the early stage of plasmodium yoelii infection in susceptible balb/c mice. | protective immunity against murine malaria infection depends largely on the establishment of effective th1 immune response during the early stages of infection. experimental data suggest that the death of plasmodium yoelii 17xl (py 17xl) susceptible balb/c mice results from the suppression of th1 immune response mediated by cd4+cd25+foxp3+ regulatory t cells (tregs). however, the mechanism by which tregs regulate th1 immune response is poorly understood. since immunity is initiated by dendritic ... | 2009 | 20128236 |
| suppressive and additive effects in protection mediated by combinations of monoclonal antibodies specific for merozoite surface protein 1 of plasmodium yoelii. | the merozoite surface protein (msp)-1 is a target antigen of protective immunity and a malaria vaccine candidate. the nature of this protective immune response warrants further investigation: although specific antibody is thought to play a major role, the mechanisms of protection are still unclear. monoclonal antibodies (mabs) specific for the c-terminus of msp-1 from plasmodium yoelii have been shown previously to provide protection against challenge infection when administered by passive immun ... | 2010 | 20146804 |
| structural determination of functional units of the nucleotide binding domain (nbd94) of the reticulocyte binding protein py235 of plasmodium yoelii. | invasion of the red blood cells (rbc) by the merozoite of malaria parasites involves a large number of receptor ligand interactions. the reticulocyte binding protein homologue family (rh) plays an important role in erythrocyte recognition as well as virulence. recently, it has been shown that members of rh in addition to receptor binding may also have a role as atp/adp sensor. a 94 kda region named nucleotide-binding domain 94 (nbd94) of plasmodium yoelii ym, representative of the putative nucle ... | 2010 | 20161776 |
| helminth infection impairs the immunogenicity of a plasmodium falciparum dna vaccine, but not irradiated sporozoites, in mice. | development of an effective vaccine against malaria remains a priority. however, a significant number of individuals living in tropical areas are also likely to be co-infected with helminths, which are known to adversely affect immune responses to a number of different existing vaccines. here we compare the response to two prototype malaria vaccines: a transmission blocking dna vaccine based on pfs25, and a pre-erythrocytic malaria vaccine based on irradiated sporozoites in mice infected with th ... | 2010 | 20188676 |
| dual effect of plasmodium-infected erythrocytes on dendritic cell maturation. | infection with plasmodium is the cause of malaria, a disease characterized by a high inflammatory response in the blood. dendritic cells (dc) participate in both adaptive and innate immune responses, influencing the generation of inflammatory responses. dc can be activated through different receptors, which recognize specific molecules in microbes and induce the maturation of dc. | 2010 | 20193084 |
| pyrimethamine induces oxidative stress in plasmodium yoelii 17xl-infected mice: a novel immunomodulatory mechanism of action for an old antimalarial drug? | pyrimethamine is an antimalarial drug that has also been used successfully to treat autoimmune diseases such as lymphoproliferative syndrome. in this work, the effect of pyrimethamine (pyr) on the production of free radicals in malaria-infected mice was studied to better understand the drug's immunomodulatory properties. balb/c and cba/ca mice were infected with plasmodium yoelii 17xl. seven days after infection, mice were treated with pyr or vehicle and sacrificed 24h later. treatment with pyr ... | 2010 | 20193682 |
| minimal role for the circumsporozoite protein in the induction of sterile immunity by vaccination with live rodent malaria sporozoites. | immunization with live plasmodium sporozoites under chloroquine prophylaxis (spz plus cq) induces sterile immunity against sporozoite challenge in rodents and, more importantly, in humans. full protection is obtained with substantially fewer parasites than with the classic immunization with radiation-attenuated sporozoites. the sterile protection observed comprised a massive reduction in the hepatic parasite load and an additional effect at the blood stage level. differences in the immune respon ... | 2010 | 20194600 |
| plasmodium falciparum pf10_0164 (etramp10.3) is an essential parasitophorous vacuole and exported protein in blood stages. | upregulated in infectious sporozoites gene 4 (uis4) encodes a parasitophorous vacuole membrane protein expressed in the sporozoite and liver stages of rodent malaria parasites. parasites that lack uis4 arrest in early liver-stage development, and vaccination of mice with uis4(-) sporozoites confers sterile protection against challenge with infectious sporozoites. currently, it remains unclear whether an ortholog of uis4 is carried in the human malaria parasite plasmodium falciparum, although the ... | 2010 | 20228203 |
| [inhibition of plasmodium yoelii circumsporozoite protein on the activation of nuclear transcription factor in hepatoma cells stimulated by tnf-alpha]. | to investigate on the effect of plasmodium yoelii (by265 strain) circumsporozoite protein (csp) on the activation of nuclear transcription factor kb (nf-kb) in hepatoma cells (hepg2) stimulated by tnf-alpha. | 2009 | 20232624 |
| [recombinant plasmodium yoelii expressing green fluorescent protein in erythrocytic and mosquito stages]. | to generate recombinant plasmodium yoelii by265 strain which can express green fluorescent protein (gfp) in erythrocytic and mosquito stages. | 2009 | 20232630 |
| small variant surface antigens and plasmodium evasion of immunity. | antigenic variation at the plasmodium-infected erythrocyte surface plays a critical role in malaria disease severity and host immune evasion. our current understanding of the role of plasmodium variant surface antigens in antigenic variation and immune evasion is largely limited to the extensive work carried out on the plasmodium falciparum var gene family. although homologues of var genes are not present in other malaria species, small variant gene families comprising the rif and stevor genes i ... | 2010 | 20353305 |
| parasitaemia levels in plasmodium chabaudi infected-mice modify ifn-gamma and il-10 expression after a homologous or heterologous challenge. | cb6f1 mice infected with the nonlethal plasmodium chabaudi chabaudi as suffer parasitaemia levels up to 40% (full parasitaemia, fp) and develop both homologous and heterologous (against the lethal plasmodium yoelii 17xl) protective immunity. however, if mice are treated with anti-malarial drug when parasitaemia is below 10% (low parasitaemia, lp), they only develop homologous immunity. for the better understanding of this interesting dissociation related to the degree of parasitaemia, in this wo ... | 2010 | 20398227 |
| alpha-tocopherol transfer protein disruption confers resistance to malarial infection in mice. | various factors impact the severity of malaria, including the nutritional status of the host. vitamin e, an intra and extracellular anti-oxidant, is one such nutrient whose absence was shown previously to negatively affect plasmodium development. however, mechanisms of this plasmodium inhibition, in addition to means by which to exploit this finding as a therapeutic strategy, remain unclear. | 2010 | 20403155 |
| transcriptional analysis of the pre-erythrocytic stages of the rodent malaria parasite, plasmodium yoelii. | the molecular biology of the clinically silent pre-erythrocytic stages of mammalian plasmodium spp, composed of both the sporozoite and liver stages, has remained largely uncharacterized. improved understanding of the biological processes required for progression through the pre-erythrocytic stages could lead to the identification of novel drug and vaccine targets. to gain insights into the molecular events that occur during the pre-erythrocytic stages of plasmodium, comparative transcriptional ... | 2010 | 20422005 |
| immunogenicity and protective efficacy of a recombinant yellow fever vaccine against the murine malarial parasite plasmodium yoelii. | the live-attenuated yellow fever vaccine (yf17d) is one of the safest and most effective vaccines available today. here, yf17d was genetically altered to express the circumsporozoite protein (csp) from the murine malarial parasite plasmodium yoelii. reconstituted recombinant virus was viable and exhibited robust csp expression. immunization of naïve mice resulted in extensive proliferation of adoptively transferred csp-specific transgenic cd8(+) t-cells. a single immunization of naïve mice with ... | 2010 | 20451637 |
| plasmodium pyruvate dehydrogenase activity is only essential for the parasite's progression from liver infection to blood infection. | plasmodium parasites possess a single pyruvate dehydrogenase (pdh) enzyme complex that is localized to the plastid-like organelle known as the apicoplast. unlike most eukaryotes, plasmodium parasites lack a mitochondrial pdh. the pdh complex catalyses the conversion of pyruvate to acetyl-coa, an important precursor for the tricarboxylic acid cycle and type ii fatty acid synthesis (fas ii). in this study, using a rodent malaria model, we show that the pdh e1 alpha and e3 subunits colocalize with ... | 2010 | 20487290 |
| plasmodium chabaudi chabaudi malaria parasites can develop stable resistance to atovaquone with a mutation in the cytochrome b gene. | plasmodium falciparum, has developed resistance to many of the drugs in use. the recommended treatment policy is now to use drug combinations. the atovaquone-proguanil (ap) drug combination, is one of the treatment and prophylaxis options. atovaquone (atq) exerts its action by inhibiting plasmodial mitochondria electron transport at the level of the cytochrome bc1 complex. plasmodium falciparum in vitro resistance to atq has been associated with specific point mutations in the region spanning co ... | 2010 | 20492669 |
| inhibition of plasmodium sporozoites infection by targeting the host cell. | there is a great need of new drugs against malaria because of the increasing spread of parasite resistance against the most commonly used drugs in the field. we found that monensin, a common veterinary antibiotic, has a strong inhibitory effect in plasmodium berghei and plasmodium yoelii sporozoites hepatocyte infection in vitro. infection of host cells by another apicomplexan parasite with a similar mechanism of host cell invasion, toxoplasma tachyzoites, was also inhibited. treatment of mice w ... | 2010 | 20493847 |
| plasmodium yoelii: influence of immune modulators on the development of the liver stage. | plasmodium sporozoites suppress the respiratory burst and antigen presentation of kupffer cells, which are regarded as the portal of invasion into hepatocytes. it is not known whether immune modulation of kupffer cells can affect the liver stage. in the present study, we found that sporozoites inoculated into wistar rats could be detected in the liver, spleen, and lung; however, most sporozoites were arrested in the liver. sporozoites were captured by kupffer cells lined with endothelial cells i ... | 2010 | 20493849 |
| distinct host-related dendritic cell responses during the early stage of plasmodium yoelii infection in susceptible and resistant mice. | the diverse outcomes of experimental murine infection with plasmodium parasites, ranging from spontaneous cure to death, depend largely on the establishment of an effective th1 immune response during the early stages of infection. however, the molecular and cellular factors responsible for the induction and regulation of this response are poorly understood. as immunity is initiated by dendritic cells (dcs), we compared their phenotype and function during the early stages of infection with plasmo ... | 2010 | 20500661 |
| efficient phagosomal maturation and degradation of plasmodium-infected erythrocytes by dendritic cells and macrophages. | dendritic cells (dc) and macrophages phagocytose pathogens and degrade them in their phagosomes to allow for proper presentation of foreign antigens to other cells of the immune system. the plasmodium parasite, causative agent of malaria, infects rbc that are phagocytosed by dc and macrophages during the course of infection. under specific conditions, the functionality of these cells can be affected by phagocytosis of plasmodium-infected rbc. we investigated whether phagosomal maturation and deg ... | 2010 | 20500669 |
| comparison of plasmodium berghei challenge models for the evaluation of pre-erythrocytic malaria vaccines and their effect on perceived vaccine efficacy. | the immunological mechanisms responsible for protection against malaria infection vary among plasmodium species, host species and the developmental stage of parasite, and are poorly understood. a challenge with live parasites is the most relevant approach to testing the efficacy of experimental malaria vaccines. nevertheless, in the mouse models of plasmodium berghei and plasmodium yoelii, parasites are usually delivered by intravenous injection. this route is highly artificial and particularly ... | 2010 | 20507620 |
| cognitive dysfunction is sustained after rescue therapy in experimental cerebral malaria, and is reduced by additive antioxidant therapy. | neurological impairments are frequently detected in children surviving cerebral malaria (cm), the most severe neurological complication of infection with plasmodium falciparum. the pathophysiology and therapy of long lasting cognitive deficits in malaria patients after treatment of the parasitic disease is a critical area of investigation. in the present study we used several models of experimental malaria with differential features to investigate persistent cognitive damage after rescue treatme ... | 2010 | 20585569 |
| 6-(4'-aryloxy-phenyl)vinyl-1,2,4-trioxanes: a new series of orally active peroxides effective against multidrug-resistant plasmodium yoelii in swiss mice. | a new series of 6-(4'-aryloxy-phenyl)vinyl-1,2,4-trioxanes 10a-d, 11a-d, and 12a-d have been synthesized and evaluated for their antimalarial activity against multidrug-resistant plasmodium yoelii in swiss mice by oral route. trioxanes 10b and 10c, the two most active compounds of the series, provided 100% protection to the infected mice at 48 mg/kg x 4 days. clinically useful drug beta-arteether provided 100% and 20% protection at 48 mg/kg x 4 days and 24 mg/kg x 4 days, respectively, in this m ... | 2010 | 20598529 |
| plasmodium yoelii: correlation of tep1 with mosquito melanization induced by nitroquine. | the antimalarial drug nitroquine is not only an effective antimalarial drug, it is also able to induce the melanization of plasmodium species. however, the molecular mechanisms of the recognition reaction induced by this drug remain unclear. silencing of thioester-containing protein-1 (tep1) significantly compromised the ability of anopheles gambiae to melanize the plasmodium, leading to investigation of the involvement of a. stephensi tep1 in melanization induced by nitroquine. this study shows ... | 2011 | 20599985 |
| characterization of immune responses to single or mixed infections with p. yoelii 17xl and p. chabaudi as in different strains of mice. | the outcome of plasmodium yoelii 17xl (p.y17xl)-infected balb/c and dba/2 mice, ranging from death to spontaneous cure, depends largely on the establishment of effective th1 and th2 responses and a successful switch between th1 and th2 responses, as well as appropriate functioning of cd4(+)cd25(+)foxp3(+)regulatory t cells (tregs). the infection with another malaria-causing parasite, plasmodium chabaudi as (p.cas), leads to a different outcome in balb/c and dba/2 mice compared to mice infected w ... | 2010 | 20609420 |
| analysis of innate defences against plasmodium falciparum in immunodeficient mice. | mice with genetic deficiencies in adaptive immunity are used for the grafting of human cells or pathogens, to study human diseases, however, the innate immune responses to xenografts in these mice has received little attention. using the nod/scid plasmodium falciparum mouse model an analysis of innate defences responsible for the substantial control of p. falciparum which remains in such mice, was performed. | 2010 | 20618960 |
| protective immune responses elicited by immunization with a chimeric blood-stage malaria vaccine persist but are not boosted by plasmodium yoelii challenge infection. | an efficacious malaria vaccine remains elusive despite concerted efforts. using the plasmodium yoelii murine model, we previously reported that immunization with the c-terminal 19 kda domain of merozoite surface protein 1 (msp1(19)) fused to full-length msp8 protected against lethal p. yoelii 17xl, well beyond that achieved by single or combined immunizations with the component antigens. here, we continue the evaluation of the chimeric pymsp1/8 vaccine. we show that immunization with rpymsp1/8 v ... | 2010 | 20709001 |
| selection and identification of malaria vaccine target molecule using bioinformatics and dna vaccination. | following a genome-wide search for a blood stage malaria dna-based vaccine using web-based bioinformatic tools, 29 genes from the annotated plasmodium yoelii genome sequence (www.plasmodb.org and www.tigr.org) were identified as encoding gpi-anchored proteins. target genes were those with orthologues in p. falciparum, containing an n-terminal signal sequence containing hydrophobic amino acid stretch and signal p criteria, a transmembrane-like domain and gpi anchor motif. focusing on the blood st ... | 2010 | 20709002 |
| a complementary role for the tetraspanins cd37 and tssc6 in cellular immunity. | the cooperative nature of tetraspanin-tetraspanin interactions in membrane organization suggests functional overlap is likely to be important in tetraspanin biology. previous functional studies of the tetraspanins cd37 and tssc6 in the immune system found that both cd37 and tssc6 regulate t cell proliferative responses in vitro. cd37(-/-) mice also displayed a hyper-stimulatory dendritic cell phenotype and dysregulated humoral responses. in this study, we characterize "double knockout" mice (cd3 ... | 2010 | 20709950 |
| in vivo antimalarial activities of glycoalkaloids isolated from solanaceae plants. | malaria is one of the most common and serious protozoan tropical diseases. multi-drug resistance remains pervasive, necessitating the continuous development of new antimalarial agents. | 2010 | 20731554 |
| replacing adenoviral vector hvr1 with a malaria b cell epitope improves immunogenicity and circumvents preexisting immunity to adenovirus in mice. | although adenovirus (ad) has been regarded as an excellent vaccine vector, there are 2 major drawbacks to using this platform: (a) ad-based vaccines induce a relatively weak humoral response against encoded transgenes, and (b) preexisting immunity to ad is highly prevalent among the general population. to overcome these obstacles, we constructed an ad-based malaria vaccine by inserting a b cell epitope derived from a plasmodium yoelii circumsporozoite (cs) protein (referred to as the pycs-b epit ... | 2010 | 20811151 |
| elevated levels of the plasmodium yoelii homologue of macrophage migration inhibitory factor attenuate blood-stage malaria. | the excessive production of proinflammatory cytokines plays a significant role in the pathogenesis of severe malaria. mammalian macrophage migration inhibitory factor (mif) (mmif) is an immune mediator that promotes a sustained proinflammatory response by inhibiting the glucocorticoid-mediated downregulation of inflammation. in addition, plasmodium parasites also encode a homologue of mammalian mif that is expressed in asexual-stage parasites. we used the plasmodium yoelii murine model to study ... | 2010 | 20837716 |
| 2-hexadecynoic acid inhibits plasmodial fas-ii enzymes and arrests erythrocytic and liver stage plasmodium infections. | acetylenic fatty acids are known to display several biological activities, but their antimalarial activity has remained unexplored. in this study, we synthesized the 2-, 5-, 6-, and 9-hexadecynoic acids (hdas) and evaluated their in vitro activity against erythrocytic (blood) stages of plasmodium falciparum and liver stages of plasmodium yoelii infections. since the type ii fatty acid biosynthesis pathway (pffas-ii) has recently been shown to be indispensable for liver stage malaria parasites, t ... | 2010 | 20855214 |
| strain-specific spleen remodelling in plasmodium yoelii infections in balb/c mice facilitates adherence and spleen macrophage-clearance escape. | knowledge of the dynamic features of the processes driven by malaria parasites in the spleen is lacking. to gain insight into the function and structure of the spleen in malaria, we have implemented intravital microscopy and magnetic resonance imaging of the mouse spleen in experimental infections with non-lethal (17x) and lethal (17xl) plasmodium yoelii strains. noticeably, there was higher parasite accumulation, reduced motility, loss of directionality, increased residence time and altered mag ... | 2010 | 20923452 |
| transgenic plasmodium that expresses hiv-1 gag elicits immunity and protects mice against vaccinia virus-gag and malarial parasites. | malaria and human immunodeficiency virus type 1 (hiv-1) infection overlap in many regions of the world. our goal was to determine the feasibility of developing transgenic plasmodium berghei that expresses hiv-1 gag, pbgag, as a conceptual bivalent vaccine against both hiv-1 infection and malaria. immunization of mice with pbgag induced specific responses to the hiv-1 gag. importantly, mice vaccinated with pbgag were significantly protected from challenge with vaccinia virus-gag (vv-gag) with an ... | 2010 | 20933565 |
| synthesis and antimalarial assessment of a new series of orally active amino-functionalized spiro 1,2,4-trioxanes. | keto-trioxanes 7a-d, easily accessible in two steps from allylic alcohols 5a-d, underwent reductive amination with substituted anilines to furnish amino-functionalized trioxanes 8a-i, 9a-i, 10a-i, and 11a-i. all these new trioxanes were assessed for their oral antimalarial activity against multidrug-resistant plasmodium yoelii nigeriensis in swiss mice. 2-naphthalene-based trioxanes 9c and 9i, the most active compounds of the series, provided 100% protection to the malaria-infected mice at 24 mg ... | 2010 | 20936847 |