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the requirement for potent adjuvants to enhance the immunogenicity and protective efficacy of protein vaccines can be overcome by prior immunization with a recombinant adenovirus.a central goal in vaccinology is the induction of high and sustained ab responses. protein-in-adjuvant formulations are commonly used to achieve such responses. however, their clinical development can be limited by the reactogenicity of some of the most potent preclinical adjuvants and the cost and complexity of licensing new adjuvants for human use. also, few adjuvants induce strong cellular immunity, which is important for protection against many diseases, such as malaria. we compared classica ...201121813775
tricomponent immunopotentiating system (tips) as a novel molecular design strategy for malaria vaccine development.creation of subunit vaccines to prevent malaria infection has been hampered by the intrinsic weak immunogenicity of the recombinant antigens. we have developed a novel strategy to increase immune responses by creating genetic protein fusions to target specific antigen-presenting cells (apcs). the fusion complex was composed of three physically linked molecular entities: (i) a vaccine antigen, (ii) a multimeric a-helical coiled-coil core, and (iii) an apc-targeting ligand linked to the core via a ...201121807905
identification of non-csp antigens bearing cd8 epitopes in mice immunized with irradiated sporozoites.immunization of balb/c mice with irradiated sporozoites (irsp) of plasmodium yoelii can lead to sterile immunity. the circumsporozoite protein (csp) plays a dominant role in protection. nevertheless after hyper-immunization with irsp, complete protection is obtained in csp-transgenic balb/c mice that are t-cell tolerant to the csp and cannot produce antibodies [csp-tg/jht(-/-)]. this protection is mediated exclusively by cd8(+) t cells [1]. to identify the non-csp protective t cell antigens, we ...201121807053
the effect of helminth co-infection on malaria in mice: a meta-analysis.the question of how helminths affect the course of concurrent malaria infection has attracted much interest in recent years. in particular, it has been suggested that by creating an anti-inflammatory immune environment, helminth co-infection may dampen both protective and immunopathological responses to malaria parasites, thus altering malaria infection dynamics and disease severity. both synergistic and antagonistic interactions are reported in the literature, and the causes of variation among ...201121777589
the antiplasmodial effect of the extracts and formulated capsules of phyllanthus amarus on plasmodium yoelii infection in mice.to investigate the antiplasmodial activity of the extracts of phyllanthus amarus (p. amarus) on plasmodium yoelii (p. yoelii) (a resistant malaria parasite strain used in animal studies) infection in mice.201121771471
clarithromycin, a cytochrome p450 inhibitor, can reverse mefloquine resistance in plasmodium yoelii nigeriensis- infected swiss mice.summaryduring the last 2 decades there have been numerous reports of the emergence of mefloquine resistance in southeast asia and nearly 50% resistance is reported in thailand. a world health organization report (2001) considers mefloquine as an important component of act (artesunate+mefloquine) which is the first line of treatment for the control of uncomplicated/multi-drug resistant (mdr) plasmodium falciparum malaria. in view of the emergence of resistance towards this drug, it is proposed to ...201121756423
etiopathogenesis of burkitt's lymphoma: a lesson from a bl-like in cd1 mouse immune to plasmodium yoelii yoelii.abstract:201121740585
chemotherapeutic interaction between khaya grandifoliola (welw) cdc stem bark extract and two anti-malarial drugs in mice.in malarial endemic countries especially in the tropics, conventional antimalarial drugs are used with herbal remedies either concurrently or successively. khaya grandifoliola is one of such popular herbs used in the treatment of malaria.various doses of ethanol extract of k. grandifoliola stem bark (50-400 mg/kg/day) were administered orally to swiss albino mice infected with plasmodium yoelii nigerense. a dose of 100 mg/kg/day of the extract was also combined with 2.5 mg/kg/day of chloroquine ...201021731168
linkage maps from multiple genetic crosses and loci linked to growth-related virulent phenotype in plasmodium yoelii.plasmodium yoelii is an excellent model for studying malaria pathogenesis that is often intractable to investigate using human parasites; however, genetic studies of the parasite have been hindered by lack of genome-wide linkage resources. here, we performed 14 genetic crosses between three pairs of p. yoelii clones/subspecies, isolated 75 independent recombinant progeny from the crosses, and constructed a high-resolution linkage map for this parasite. microsatellite genotypes from the progeny f ...201121690382
cytokine profile of murine malaria: stage-related production of inflammatory and anti-inflammatory cytokines.balance between inflammatory and anti-inflammatory cytokines may be important in malaria presentation and outcome. to clarify cytokine interactions that produce pathology of malaria and control infection, c57bl/6 mice were infected with 10(4) parasitized rbcs from a non-lethal strain of plasmodium yoelii. kinetics was monitored showing the course of parasitemia, and cytokines were determined by rt-pcr from liver and spleen tissues. inflammatory cytokines such as interferon-+¦ (ifn+¦), interleuki ...201121673450
changes in parasite virulence induced by the disruption of a single member of the 235 kda rhoptry protein multigene family of plasmodium yoelii.invasion of the erythrocyte by the merozoites of the malaria parasite is a complex process involving a range of receptor-ligand interactions. two protein families termed erythrocyte binding like (ebl) proteins and reticulocyte binding protein homologues (rh) play an important role in host cell recognition by the merozoite. in the rodent malaria parasite, plasmodium yoelii, the 235 kda rhoptry proteins (py235) are coded for by a multigene family and are members of the rh. in p. yoelii py235 as we ...201121625465
oral delivery of curcumin bound to chitosan nanoparticles cured plasmodium yoelii infected mice.curcumin has been shown to have anti malarial activity, but its poor bioavailability and chemical instability has hindered its development as a drug. we have bound curcumin to chitosan nanoparticles to improve its bioavailability and chemical stability. we found that curcumin bound to chitosan nanoparticles did not degrade that rapidly in comparison to free curcumin when such particles were incubated in mouse plasma in vitro at room temperature. the uptake of bound curcumin from chitosan nanopar ...201121619927
antiplasmodial activity of artecyclopentyl mether a new artemisinin derivative and its effect on pathogenesis in plasmodium yoelii nigeriensis infected mice.in an effort to evaluate novel derivatives from artemisinin, possessing potential antimalarial activity, a new derivative artecyclopentyl mether (cpm-1) was derivatized and evaluated for its dose-dependent efficacy in plasmodium yoelii nigeriensis infected mice. the survivability of mice at 7.5 mg/kg was >28 days with negligible parasitaemia and recovered anemia (66.16-72.62%). artecyclopentyl mether was also found to modulate the pro- and anti-inflammatory cytokines (ifn-γ, 39.64-56.92%; tnf, 4 ...201121541755
parasitostatic effect of maslinic acid. ii. survival increase and immune protection in lethal plasmodium yoelii-infected mice.abstract:201121518429
daily plasmodium yoelii infective mosquito bites do not generate protection or suppress previous immunity against the liver stage.abstract:201121501513
structural characterization of the erythrocyte binding domain of the reticulocyte binding protein homologues family of plasmodium yoelii.invasion of the host cell by the malaria parasite is a key step for parasite survival and the only stage of its life cycle where the parasite is extracellular, and is therefore a target for an antimalaria intervention strategy. multiple members of the reticulocyte binding protein homologues (rh) family are found in all plasmodia and shown to bind to host red blood cells directly. in the study here we have delineated the erythrocyte binding domain of one member of the rh family, termed py235 from ...201121482683
a critical role for phagocytosis in resistance to malaria in iron-deficient mice.both iron-deficient anemia (ida) and malaria remain a threat to children in developing countries. children with ida are resistant to malaria, but the reasons for this are unknown. in this study, we addressed the mechanisms underlying the protection against malaria observed in ida individuals using a rodent malaria parasite, plasmodium yoelii (py). we showed that the intra-erythrocytic proliferation and amplification of py parasites were not suppressed in ida erythrocytes and immune responses spe ...201121469097
identification of two new protective pre-erythrocytic malaria vaccine antigen candidates.despite years of effort, a licensed malaria vaccine is not yet available. one of the obstacles facing the development of a malaria vaccine is the extensive heterogeneity of many of the current malaria vaccine antigens. to counteract this antigenic diversity, an effective malaria vaccine may need to elicit an immune response against multiple malaria antigens, thereby limiting the negative impact of variability in any one antigen. since most of the malaria vaccine antigens that have been evaluated ...201121410955
[cryopreservation of plasmodia with malaria models and establishment of a cryobank.]objective: cryopreservation is simply a method of keeping living cells frozen with the chance of regaining cellular viability, functions and antigenic structures whenever required, after heating. methods: in the present study, dimethyl sulphoxide (dmso) was mixed with the red blood cells having 20% of parasitemia obtained from the mice infected with plasmodium yoelii and plasmodium berghei at a final concentration of 15%. for cryopreservation: both test tubes containing each plasmodium species w ...201021391181
targeted disruption of py235ebp-1: invasion of erythrocytes by plasmodium yoelii using an alternative py235 erythrocyte binding protein.plasmodium yoelii ym asexual blood stage parasites express multiple members of the py235 gene family, part of the super-family of genes including those coding for plasmodium vivax reticulocyte binding proteins and plasmodium falciparum rh proteins. we previously identified a py235 erythrocyte binding protein (py235ebp-1, encoded by the py01365 gene) that is recognized by protective mab 25.77. proteins recognized by a second protective mab 25.37 have been identified by mass spectrometry and are e ...201121379566
nmr solution structure of nbd94(483-502) of the nucleotide-binding domain of the plasmodium yoelii reticulocyte-binding protein py235.invasion of the erythrocyte by the invasive form of the malaria parasite, the merozoite, is a complex process involving numerous parasite proteins. the reticulocyte-binding protein homologues (rh) family of merozoite proteins has been previously shown to play an important role in the invasion process. previously, it has been shown that the rh proteins of plasmodium yoelii, py235, play a role as an atp/adp sensor. binding of py235 to the erythrocyte surface is increased in the presence of atp, wh ...201121366672
superparamagnetic nanoparticles for effective delivery of malaria dna vaccine.low efficiency is often observed in the delivery of dna vaccines. the use of superparamagnetic nanoparticles (spions) to deliver genes via magnetofection could improve transfection efficiency and target the vector to its desired locality. here, magnetofection was used to enhance the delivery of a malaria dna vaccine encoding plasmodium yoelii merozoite surface protein msp1(19) (vr1020-pymsp1(19)) that plays a critical role in plasmodium immunity. the plasmid dna (pdna) containing membrane associ ...201121361304
effect of nanoparticle coating on the immunogenicity of plasmid dna vaccine encoding p. yoelii msp-1 c-terminal.in order to assess a new strategy for dna vaccine formulation and delivery, plasmid encoding plasmodium yoelii msp-1 c-terminal was formulated with newly designed nanoparticle-an anionic ternary complex of polyethylenimine and ?-polyglutamic acid (pvax-msp-1/pei/?-pga), and intravenously administered to c57bl/6 mice in four different doses, three times at 3-week interval. antibody response as determined by elisa, ifa and western blot, was dose-dependent and subsequent challenge with 10(5)p. yoel ...201121354479
in vivo antimalarial activity of ginseng extracts.novel antimalarial agents are in demand due to the emergence of multidrug resistant strains. ginseng, a medicinal plant with antiparasitic activity, contains components that can be used to treat the tropical disease malaria.201121323481
sap1 is a critical post-transcriptional regulator of infectivity in malaria parasite sporozoite stages.plasmodium salivary gland sporozoites upregulate expression of a unique subset of genes, collectively called the uis (upregulated in infectious sporozoites). many uis were shown to be essential for early liver stage development, although little is known about their regulation. we previously identified a conserved sporozoite-specific protein, sap1, which has an essential role in plasmodium liver infection. targeted deletion of sap1 in plasmodium yoelii caused the depletion of a number of selectiv ...201021299648
site-specific integration and expression of an anti-malarial gene in transgenic anopheles gambiae significantly reduces plasmodium infections.diseases transmitted by mosquitoes have a devastating impact on global health and this is worsening due to difficulties with existing control measures and climate change. genetically modified mosquitoes that are refractory to disease transmission are seen as having great potential in the delivery of novel control strategies. historically the genetic modification of insects has relied upon transposable elements which have many limitations despite their successful use. to circumvent these limitati ...201121283619
in vitro biotransformation, in vivo efficacy and pharmacokinetics of antimalarial chalcones.4'-n-butoxy-2,4-dimethoxy-chalcone (mbc) has been described as protecting mice from an otherwise lethal infection with plasmodium yoelii when dosed orally at 50 mg/kg/dose, daily for 5 days. in contrast, we found that oral dosing of mbc at 640 mg/kg/dose, daily for 5 days, failed to extend the survivability of p. berghei-infected mice. the timing of compound administration and metabolic activation likely contribute to the outcome of efficacy testing in vivo. microsomal digest of mbc yielded 4'-n ...201121282967
protocol for production of a genetic cross of the rodent malaria parasites.variation in response to antimalarial drugs and in pathogenicity of malaria parasites is of biologic and medical importance. linkage mapping has led to successful identification of genes or loci underlying various traits in malaria parasites of rodents and humans. the malaria parasite plasmodium yoelii is one of many malaria species isolated from wild african rodents and has been adapted to grow in laboratories. this species reproduces many of the biologic characteristics of the human malaria pa ...201121248692
cd4+ t cells modulate expansion and survival but not functional properties of effector and memory cd8+ t cells induced by malaria sporozoites.cd4(+) helper t cells are critical orchestrators of immune responses to infection and vaccination. during primary responses, naïve cd8(+) t cells may need "cd4 help" for optimal development of memory populations. the immunological factors attributed to cd4 help depend on the context of immunization and vary depending on the priming system. in response to immunization with radiation-attenuated plasmodium yoelii sporozoites, cd8(+) t cells in balb/c mice fail to generate large numbers of effector ...201121245909
the intradermal route for inoculation of sporozoites of rodent malaria parasites for immunological studies.rodent malaria parasites are commonly used for investigations into the immunology of pre-erythrocytic stage malaria infection, as sporozoites can be easily produced in the laboratory. in the majority of past immunological studies using this system, sporozoites are inoculated into mice via the intravenous (iv) route. in natural situations, however, sporozoites are deposited into the skin by the bite of anopheline mosquitoes, and it is likely that the immunological response to such natural intrade ...201121226727
fret peptides reveal differential proteolytic activation in intraerythrocytic stages of the malaria parasites plasmodium berghei and plasmodium yoelii.malaria is still a major health problem in developing countries. it is caused by the protist parasite plasmodium, in which proteases are activated during the cell cycle. ca(2+) is a ubiquitous signalling ion that appears to regulate protease activity through changes in its intracellular concentration. proteases are crucial to plasmodium development, but the role of ca(2+) in their activity is not fully understood. here we investigated the role of ca(2+) in protease modulation among rodent plasmo ...201021168413
intradermal immunization of mice with radiation-attenuated sporozoites of plasmodium yoelii induces effective protective immunity.intravenous injection of mice with attenuated plasmodium berghei sporozoites induces sterile immunity to challenge with viable sporozoites. non-intravenous routes have been reported to yield poor immunity. because intravenous immunization has been considered to be unacceptable for large scale vaccination of humans, assessment was made of the results of intradermal immunization of mice with plasmodium yoelii, a rodent malaria parasite whose infectivity resembles that of human malaria.201021159170
antimalarial and antioxidant activities of methanolic extract of nigella sativa seeds (black cumin) in mice infected with plasmodium yoelli nigeriensis.the antimalarial and antioxidant activities of methanolic extract of nigella sativa seeds (mens) were investigated against established malaria infection in vivo using swiss albino mice. the antimalarial activity of the extract against plasmodium yoelli nigeriensis (p. yoelli) was assessed using the rane test procedure. chloroquine (cq)-treated group served as positive control. the extract, at a dose of 1.25 g/kg body weight significantly (p < 0.05) suppressed p. yoelli infection in the mice by 9 ...201021153838
crystallographic studies of the coupling segment nbd94(674-781) of the nucleotide-binding domain of the plasmodium yoelii reticulocyte-binding protein py235.the plasmodium yoelii reticulocyte-binding protein py235 has a role as an atp/adp sensor. the sensor domain of py235 is called nbd94; it consists of at least three functional regions, the nucleotide-binding region (nbd94(444-547)), hinge region (nbd94(566-663)) and c-terminal coupling region (nbd94(674-781)), and has been proposed to link atp/adp binding to the interaction of py235 with the red blood cell. here, nbd94(674-781) was cloned, expressed and purified to high purity. the monodisperse p ...201021139212
protection against malaria is conferred by passive transferring rabbit f(ab)(2)' antibody fragments, induced by plasmodium falciparum msp-1 site-directed designed pseudopeptide-bsa conjugates assessed in a rodent model.f(ab)(2)'-immunoglobulin (ig) fragments induced by site-directed designed immunogens are emerging as novel tools of potential utility in the treatment of clinical episodes of transmissible diseases such as malaria. immunogens based on reduced amide pseudopeptides based on site-directed molecular modifications represent structural probes that could be considered as novel vaccine candidates, as we have previously demonstrated. we have obtained f(ab)(2)'-ig rabbit antibodies induced against the n-t ...201021131051
apoptosis of non-parasitized red blood cells in malaria: a putative mechanism involved in the pathogenesis of anaemia.severe anaemia is a common complication of plasmodium falciparum malaria in hyperendemic regions. premature elimination of non-parasitized red blood cells (nrbc) has been considered as one mechanism involved in the genesis of severe malaria anaemia. it has been reported that apoptosis can occur in rbc and, consequently, this cell death process could contribute to anaemia. this study was performed to evaluate the susceptibility of nrbc to apoptosis in a malaria anaemia murine model.201021126362
automated estimation of parasitaemia of plasmodium yoelii-infected mice by digital image analysis of giemsa-stained thin blood smears.parasitaemia, the percentage of infected erythrocytes, is used to measure progress of experimental plasmodium infection in infected hosts. the most widely used technique for parasitaemia determination is manual microscopic enumeration of giemsa-stained blood films. this process is onerous, time consuming and relies on the expertise of the experimenter giving rise to person-to-person variability. here the development of image-analysis software, named plasmodium autocount, which can automatically ...201021122144
caspase-12 deficiency enhances cytokine responses but does not protect against lethal plasmodium yoelii 17xl infection.to investigate the effect of caspase-12 deficiency on ifn-γ- independent control of blood-stage malaria, we compared lethal plasmodium yoelii 17xl infection in wild-type c57bl ⁄ 6j and caspase-12-/-mice. infected caspase-12-/- mice exhibited higher parasitaemia than wt mice on days 8 and 9 post-inoculation, but all wt and caspase-12-/- mice succumbed by day 10. in addition, infected caspase-12-/-mice had significantly elevated levels of ifn-γ, tnf, il-18,and il-10 in sera compared to infected wt ...201021086719
plasmodium berghei circumvents immune responses induced by merozoite surface protein 1- and apical membrane antigen 1-based vaccines.two current leading malaria blood-stage vaccine candidate antigens for plasmodium falciparum, the c-terminal region of merozoite surface protein 1 (msp1(19)) and apical membrane antigen 1 (ama1), have been prioritized because of outstanding protective efficacies achieved in a rodent malaria plasmodium yoelii model. however, p. falciparum vaccines based on these antigens have had disappointing outcomes in clinical trials. discrepancies in the vaccine efficacies observed between the p. yoelii mode ...201021060850
phenotypic and functional profiling of malaria-induced cd8 and cd4 t cells during blood-stage infection with plasmodium yoelii.it is widely accepted that antibodies and cd4 t cells play critical roles in the immune response during the blood stage of malaria, whereas the role of cd8 t cells remains controversial. here, we show that both cd8 and cd4 t cells robustly responded to an acute self-limiting blood-stage infection with plasmodium yoelii. similar to antigen-specific t cells, both cd8 and cd4 t cells showed dynamic expression of the surface proteins interleukin (il)-7r and programmed death-1 (pd-1). additionally, a ...201021039472
immunotoxicity of dibromoacetic acid administered via drinking water to female b₆c₃f₁ mice.dibromoacetic acid (dba) is a disinfection by-product commonly found in drinking water as a result of chlorination/ ozonation processes. the environmental protection agency estimates that more than 200 million people consume disinfected water in the united states. this study was conducted to evaluate the potential immunotoxicological effects of dba exposure when administered for 28 days via drinking water to b₆c₃f₁ mice, at concentrations of 125, 500, and 1000 mg/l. multiple endpoints were evalu ...201020958156
synthesis of new 4-aminoquinolines and quinoline-acridine hybrids as antimalarial agents.despite emergence of resistance to cq and other 4-aminoquinoline drugs in most of the endemic regions, research findings provide considerable support that there is still significant potential to discover new affordable, safe, and efficacious 4-aminoquinoline antimalarials. in present study, new side chain modified 4-aminoquinoline derivatives and quinoline-acridine hybrids were synthesized and evaluated in vitro against nf 54 strain of plasmodium falciparum. among the evaluated compounds, compou ...201020951034
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 ...201020936847
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 ...201020933565
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 ...201020923452
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 ...201020855214
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 ...201020837716
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 ...201020811151
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.201020731554
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 ...201020709950
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 ...201020709002
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 ...201020709001
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.201020618960
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 ...201020609420
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 ...201120599985
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 ...201020598529
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 ...201020585569
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 ...201020507620
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 ...201020500669
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 ...201020500661
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 ...201020493849
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 ...201020493847
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 ...201020492669
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 ...201020487290
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 ...201020451637
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 ...201020422005
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.201020403155
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 ...201020398227
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 ...201020353305
[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.200920232630
[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.200920232624
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 ...201020228203
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 ...201020194600
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 ...201020193682
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.201020193084
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 ...201020188676
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 ...201020161776
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 ...201020146804
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 ...200920128236
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 ...201020126610
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 ...201020101613
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 ...201020100860
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 ...201020097151
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 ( ...201020093160
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 ...201020069056
[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.200920066988
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 ...201020045029
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).201020034790
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 ...201020022412
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.200920011659
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 ...201020004020
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 ...201019935770
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 ...201019932669
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 ...201019917716
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.201019913491
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 ...201019901059
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), ...201019879998
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 ...200919879137
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 ...200919842370
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 ...200919812194
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