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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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
[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
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
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
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
daily plasmodium yoelii infective mosquito bites do not generate protection or suppress previous immunity against the liver stage.abstract:201121501513
parasitostatic effect of maslinic acid. ii. survival increase and immune protection in lethal plasmodium yoelii-infected mice.abstract:201121518429
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
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
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
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
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
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
etiopathogenesis of burkitt's lymphoma: a lesson from a bl-like in cd1 mouse immune to plasmodium yoelii yoelii.abstract:201121740585
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
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
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
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
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
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
a systematic analysis of the early transcribed membrane protein family throughout the life cycle of plasmodium yoelii.the early transcribed membrane proteins (etramps) are a family of small, highly charged transmembrane proteins unique to malaria parasites. some members of the etramp family have been localized to the parasitophorous vacuole membrane that separates the intracellular parasite from the host cell and thus presumably have a role in host-parasite interactions. although it was previously shown that two etramps are critical for rodent malaria parasite liver-stage development, the importance of most etr ...201121819513
[function of tep1 gene during plasmodium yoelii infection in anopheles dirus].to study the role of tep1 gene from anopheles dirns during plasmodium yoelii infection by rna interference.201121823319
the primase domain of pfprex is a proteolytically matured, essential enzyme of the apicoplast.the apicoplast of plasmodium is an essential organelle with its own circular genome that must be faithfully replicated and segregated to its progeny during parasite sporogony and schizogony. dna replication proteins are not encoded by its genome. instead, the replication machinery must be imported from nuclear-encoded genes. a likely apicoplast dna replication factor, pfprex, bears a bipartite leader sequence for apicoplast trafficking and contains several dna replication-related enzymatic domai ...201121856338
Combining Liver- and Blood-Stage Malaria Viral-Vectored Vaccines: Investigating Mechanisms of CD8+ T Cell Interference.Replication-deficient adenovirus and modified vaccinia virus Ankara (MVA) vectors expressing single pre-erythrocytic or blood-stage Plasmodium falciparum Ags have entered clinical testing using a heterologous prime-boost immunization approach. In this study, we investigated the utility of the same immunization regimen when combining viral vectored vaccines expressing the 42-kDa C terminus of the blood-stage Ag merozoite surface protein 1 and the pre-erythrocytic Ag circumsporozoite protein in th ...201121876036
monoclonal auto-antibodies and sera of autoimmune patients react with plasmodium falciparum and inhibit its in vitro growth.the relationship between autoimmunity and malaria is not well understood. to determine whether autoimmune responses have a protective role during malaria, we studied the pattern of reactivity to plasmodial antigens of sera from 93 patients with 14 different autoimmune diseases (aid) who were not previously exposed to malaria. sera from patients with 13 different aid reacted against plasmodium falciparum by indirect fluorescent antibody test with frequencies varying from 33-100%. in addition, ser ...201121881756
high-throughput multi-parameter flow-cytometric analysis from micro-quantities of plasmodium-infected blood.despite significant technological and conceptual advances over the last century, evaluation of the efficacy of anti-malarial vaccines or drugs continues to rely principally on direct microscopic visualisation of parasites on thick and/or thin giemsa-stained blood smears. this requires technical expertise of the microscopist, is highly subjective and error-prone, and does not account for aberrations such as anaemia. many published methods have shown that flow cytometric analysis of blood is a hig ...201121907206
plasmodium protease rom1 is important for proper formation of the parasitophorous vacuole.apicomplexans are obligate intracellular parasites that invade host cells by an active process leading to the formation of a non-fusogenic parasitophorous vacuole (pv) where the parasite replicates within the host cell. the rhomboid family of proteases cleaves substrates within their transmembrane domains and has been implicated in the invasion process. although its exact function is unknown, plasmodium rom1 is hypothesized to play a role during invasion based on its microneme localization and i ...201121909259
a new malaria antigen produces partial protection against plasmodium yoelii challenge.of all the parasitic diseases, malaria is the number one killer. despite tremendous efforts in disease control and research, nearly a million people, primarily children, still die from the disease each year, partly due to drug resistance and the lack of an effective vaccine. many parasite antigens have been identified and evaluated for vaccine development; however, none has been approved for human use. antigenic variation, complex life cycle, and inadequate understanding of the mechanisms of par ...201121915626
characterization and tissue-specific expression patterns of the plasmodium chabaudi cir multigene family.variant antigens expressed on the surface of parasitized red blood cells (prbcs) are important virulence factors of malaria parasites. whereas plasmodium falciparum erythrocyte membrane proteins 1 (pfemp1) are responsible for sequestration of mature parasites, little is known about putative ligands mediating cytoadherence to host receptors in other plasmodium species. candidates include members of the pir superfamily found in the human parasite plasmodium vivax (vir), in the simian pathogen plas ...201121929749
immunogenicity of novel nanoparticle-coated msp-1 c-terminus malaria dna vaccine using different routes of administration.an important aspect in optimizing dna vaccination is antigen delivery to the site of action. in this way, any alternative delivery system having higher transfection efficiency and eventual superior antibody production needs to be further explored. the novel nanoparticle, pdna/pei/γ-pga complex, is one of a promising delivery system, which is taken up by cells and is shown to have high transfection efficiency. the immunostimulatory effect of this novel nanoparticle (np) coated plasmid encoding pl ...201121939717
Purification and characterization of Plasmodium yoelii adenosine deaminase.Plasmodium lacks the de novo pathway for purine biosynthesis and relies exclusively on the salvage pathway. Adenosine deaminase (ADA), first enzyme of the pathway, was purified and characterized from Plasmodium yoelii, a rodent malarial species, using ion exchange and gel exclusion chromatography. The purified enzyme is a 41 kDa monomer. The enzyme showed K(m) values of 41 µM and 34 µM for adenosine and 2'-deoxyadenosine, respectively. Erythro-9-(2-hydroxy-3-nonyl) adenine competitively inhibite ...201121945268
[l-arginine enhances th1 immune response against plasmodium yoelii 17xl infection in dba/2 mice via activation of dendritic cells].to investigate the effect of l-arginine (l-arg) during blood-stage infection by p.y17xl in dba/2 mice.201121972595
b and t lymphocyte attenuator restricts the protective immune response against experimental malaria.the immune response against the blood stage of malaria has to be tightly regulated to allow for vigorous antiplasmodial activity while restraining potentially lethal immunopathologic damage to the host like cerebral malaria. coinhibitory cell surface receptors are important modulators of immune activation. b and t lymphocyte attenuator (btla) (cd272) is a coinhibitory receptor expressed by most leukocytes, with the highest expression levels on t and b cells, and is involved in the maintenance of ...201121998455
macrophage migration inhibitory factor homolog from plasmodium yoelii modulates monocyte recruitment and activation in spleen during infection.macrophage migration inhibitory factor (mif) has been shown to be involved in the pathogenesis of severe malaria. malaria parasites express an mif homolog that may play a role in regulating host immune responses, and a recent study showed that overexpression of mif reduced parasitemia in a mouse malaria model. another recent study showed migration of monocytes to the spleen contributed to the control of blood stage infection. however, there are few papers describing the effect of mif on monocyte ...201122015474
comparative histopathology of mice infected with the 17xl and 17xnl strains of plasmodium yoelii.abstract plasmodium yoelii 17xl was used to investigate the mechanism of plasmodium falciparum-caused cerebral malaria, but its histopathological effect on other mouse organs is still unclear. in the present study, histological examination was performed on mice infected with p. yoelii 17xl, and the effect of p. yoelii 17xl infection on anemia and body weight loss, as well as its lesions in the brain, liver, kidney, lung, and spleen was also investigated. p. yoelii 17xl-infected red blood cells ...201122017443
exosomes from plasmodium yoelii-infected reticulocytes protect mice from lethal infections.exosomes are 30-100-nm membrane vesicles of endocytic origin that are released after the fusion of multivesicular bodies (mvbs) with the plasma membrane. while initial studies suggested that the role of exosomes was limited to the removal of proteins during the maturation of reticulocytes to erythrocytes, recent studies indicate that they are produced by different types of cells and are involved in promoting inter-cellular communication and antigen presentation. here, we describe the isolation a ...201122046311
a single injection of 19 kda carboxy-terminal fragment of plasmodium yoelii merozoite surface protein 1 (pymsp1(19)) formulated with montanide isa and cpg odn induces protective immune response in mice.to investigate the efficacy of a vaccine formulation of the 19 kda conserved carboxyl-terminal fragment of plasmodium yoelii merozoite surface protein-1 (pymsp1(19)) formulated with cpg odn 1826 and montanide isa51 or isa720 when used to immunize mice by a single injection.201122053595
evaluation of approaches to identify the targets of cellular immunity on a proteome-wide scale.vaccine development against malaria and other complex diseases remains a challenge for the scientific community. the recent elucidation of the genome, proteome and transcriptome of many of these complex pathogens provides the basis for rational vaccine design by identifying, on a proteome-wide scale, novel target antigens that are recognized by t cells and antibodies from exposed individuals. however, there is currently no algorithm to effectively identify important target antigens from genome s ...201122096610
Merozoite surface protein-1 of Plasmodium yoelii fused via an oligosaccharide moiety of cholera toxin B subunit glycoprotein expressed in yeast induced protective immunity against lethal malaria infection in mice.Methylotrophic yeast (Pichia pastoris) secreted cholera toxin B subunit (CTB) predominantly as a biologically active pentamer (PpCTB) with identical ganglioside binding affinity profiles to that of choleragenoid. Unlike choleragenoid, however, the PpCTB did not induce a footpad edema response in mice. Of the two potential glycosylation sites (NIT(4-6) and NKT(90-92)) for this protein, a N-linked oligosaccharide was identified at Asn4. The oligosaccharide, presumed to extend from the lateral circ ...201122119928
production, characterisation and immunogenicity of a plant-made plasmodium antigen-the 19 kda c-terminal fragment of plasmodium yoelii merozoite surface protein 1.development of a safe, effective and affordable malaria vaccine is central to global disease control efforts. one of the most highly regarded proteins for inclusion in an asexual blood stage subunit vaccine is the 19-kda c-terminal fragment of merozoite surface protein 1 (msp1(19)). as production of vaccine antigens in plants can potentially overcome cost and delivery hurdles, we set out to produce msp1(19) in plants, characterise the protein and test its immunogenicity using a mouse model. plas ...201122170105
malaria impairs resistance to salmonella through heme- and heme oxygenase-dependent dysfunctional granulocyte mobilization.in sub-saharan africa, invasive nontyphoid salmonella (nts) infection is a common and often fatal complication of plasmodium falciparum infection. induction of heme oxygenase-1 (ho-1) mediates tolerance to the cytotoxic effects of heme during malarial hemolysis but might impair resistance to nts by limiting production of bactericidal reactive oxygen species. we show that co-infection of mice with plasmodium yoelii 17xnl (py17xnl) and salmonella enterica serovar typhimurium 12023 (salmonella typh ...201122179318
malaria infections do not compromise vaccine-induced immunity against tuberculosis in mice.given the considerable geographic overlap in the endemic regions for malaria and tuberculosis, it is probable that co-infections with mycobacterium tuberculosis and plasmodium species are prevalent. thus, it is quite likely that both malaria and tb vaccines may be used in the same populations in endemic areas. while novel vaccines are currently being developed and tested individually against each of these pathogens, the efficacy of these vaccines has not been evaluated in co-infection models. to ...201122205939
genome comparison of human and non-human malaria parasites reveals species subset-specific genes potentially linked to human disease.genes underlying important phenotypic differences between plasmodium species, the causative agents of malaria, are frequently found in only a subset of species and cluster at dynamically evolving subtelomeric regions of chromosomes. we hypothesized that chromosome-internal regions of plasmodium genomes harbour additional species subset-specific genes that underlie differences in human pathogenicity, human-to-human transmissibility, and human virulence. we combined sequence similarity searches wi ...201122215999
linker-based hemisuccinate derivatives of artemisinin: synthesis and antimalarial assessment against multidrug-resistant plasmodium yoelii nigeriensis in mice (1).artesunic acid 5, the hemisuccinate derivative of dihydroartemisinin 2, is the only clinically useful water-soluble derivative of artemisinin 1. however, being a lactol ester, it is rapidly hydrolyzed back to dihydroartemisinin in aqueous alkaline solution, a reaction that seriously limits its utility. a new series of potentially more stable linker-based hemisuccinate derivatives 12a-i and 14a-c have been prepared. the process involved acid-catalyzed reaction of dihydroartemisinin with various d ...201222216834
testing in mice the hypothesis that melanin is protective in malaria infections.malaria has had the largest impact of any infectious disease on shaping the human genome, exerting enormous selective pressure on genes that improve survival in severe malaria infections. modern humans originated in africa and lost skin melanization as they migrated to temperate regions of the globe. although it is well documented that loss of melanization improved cutaneous vitamin d synthesis, melanin plays an evolutionary ancient role in insect immunity to malaria and in some instances melani ...201222242171
plasmodium yoelii macrophage migration inhibitory factor is necessary for efficient liver-stage development.mammalian macrophage migration inhibitory factor (mif) is a multifaceted cytokine involved in both extracellular and intracellular functions. malaria parasites express a mif homologue that might modulate host immune responses against blood-stage parasites, but the potential importance of mif against other life cycle stages remains unstudied. in this study, we characterized the mif homologue of plasmodium yoelii throughout the life cycle, with emphasis on preerythrocytic stages. p. yoelii mif (py ...201222252874
a hybrid multistage protein vaccine induces protective immunity against murine malaria.we have previously reported the design and expression of chimeric recombinant proteins as an effective platform to deliver malaria vaccines. the erythrocytic and exoerythrocytic protein chimeras described included autologous t helper epitopes genetically linked to defined b cell epitopes. proof-of-principle studies using vaccine constructs based on the plasmodium yoelii circumsporozoite protein (csp) and p. yoelii merozoite surface protein-1 (msp-1) showed encouraging results when tested individ ...201222252877
effects of the antimalarial drugs ferroquine and artesunate on plasmodium yoelii yoelii gametocytegenesis and vectorial transmission.chemistry still has a role in the management of malaria, alongside the mosquito netting soaked in insecticide that is used increasingly, as we continue to await the long anticipated vaccine. during its cycle, the hematozoon parasite develops through three major periods. the first, malarial infection, corresponds to the intrahepatic development of infective forms from the mosquito vector; this period is not sensitive to treatment and is often asymptomatic. the period of erythrocytic schizogony is ...201122294247
intravital microscopy of the spleen: quantitative analysis of parasite mobility and blood flow.the advent of intravital microscopy in experimental rodent malaria models has allowed major advances to the knowledge of parasite-host interactions. thus, in vivo imaging of malaria parasites during pre-erythrocytic stages have revealed the active entrance of parasites into skin lymph nodes, the complete development of the parasite in the skin, and the formation of a hepatocyte-derived merosome to assure migration and release of merozoites into the blood stream. moreover, the development of indi ...201222298018
the generation and evaluation of two panels of epitope-matched mouse igg1, igg2a, igg2b and igg3 antibodies specific for plasmodium falciparum and plasmodium yoelii merozoite surface protein 1-19 (msp1(19)).murine immunoglobulin g (igg) plays an important role in mediating protective immune responses to malaria. we still know relatively little about which igg subclasses protect against this disease in mouse models, although igg2a and igg2b are considered to be the most potent and dominate in successful passive transfer experiments in rodent malarias. to explore the mechanism(s) by which the different mouse igg subclasses may mediate a protective effect, we generated mouse igg1, igg2a, igg2b and igg ...201222343045
polysaccharides from the chinese medicinal herb achyranthes bidentata enhance anti-malarial immunity during plasmodium yoelii 17xl infection in mice.clinical immunity to malaria in human populations is developed after repeated exposure to malaria. regulation and balance of host immune responses may lead to optimal immunity against malaria parasite infection. polysaccharides (abps) derived from the chinese herb ox knee achyranthes bidentata possess immuno-modulatory functions. the aim of this study is to use the rodent malaria model plasmodium yoelii 17xl (p. y17xl) to examine whether pretreatment with abps will modulate host immunity against ...201222348301
induction of ssdna-binding autoantibody secreting b cell immunity during murine malaria infection is a critical part of the protective immune responses.although it has been hypothesized that autoimmune-like phenomena may play a critical role in the protective immune responses to both human and animal malaria, there are still no evidence-based data to support this view. in this study we demonstrate that the majority of anti-single stranded (ss) dna autoantibody secreting b cells were confined to b220(+)cd21(+)cd23(-) cells and that these cells expanded significantly in the spleen of c57bl/6 mice infected with plasmodium yoelii 17x non-lethal (py ...201322361243
anti-malarial activity of geldanamycin derivatives in mice infected with plasmodium yoelii.geldanamycin (ga), a benzoquinone ansamycin antibiotic has been shown in vitro to possess anti-plasmodial activity. pharmacological activity of this drug is attributed to its ability to inhibit pfhsp90. the parasite growth arrest has been shown to be due to drug-induced blockage of the transition from ring to trophozoite stage. to further evaluate the consequences of this pharmacodynamic feature, the anti-malarial activity of ga analogs with enhanced drug properties in a plasmodium-infected anim ...201222361388
the course of a primary infection of plasmodium yoelii 17xl in both 129s1 and ifn-γ receptor-deficient mice.in the present study, we found that 129s1 mice are resistant to the infection with plasmodium yoelii 17xl, which is highly virulent and causes lethal infection in various strains of mice. in contrast, ifn-γ receptor-deficient (ifn-γr(-/-)) mice on the 129s1 background were much more susceptible than 129s1 mice with intraperitoneal infection with 1 × 10(5) parasitized erythrocytes. the mortality in 129s1 and ifn-γr(-/-) mice was 11.6 and 79.4 %, respectively. following inoculation of the parasite ...201222392138
evidence for the contribution of the hemozoin synthesis pathway of the murine plasmodium yoelii to the resistance to artemisinin-related drugs.plasmodium falciparum malaria is a major global health problem, causing approximately 780,000 deaths each year. in response to the spreading of p. falciparum drug resistance, who recommended in 2001 to use artemisinin derivatives in combination with a partner drug (called act) as first-line treatment for uncomplicated falciparum malaria, and most malaria-endemic countries have since changed their treatment policies accordingly. currently, act are often the last treatments that can effectively an ...201222403683
extracellular atp triggers proteolysis and cytosolic ca²⁺ rise in plasmodium berghei and plasmodium yoelii malaria parasites.plasmodium has a complex cell biology and it is essential to dissect the cell-signalling pathways underlying its survival within the host.201222420332
extrahepatic exoerythrocytic forms of rodent malaria parasites at the site of inoculation: clearance after immunization, susceptibility to primaquine, and contribution to blood-stage infection.plasmodium sporozoites are inoculated into the skin of the mammalian host as infected mosquitoes probe for blood. a proportion of the inoculum enters the bloodstream and goes to the liver, where the sporozoites invade hepatocytes and develop into the next life cycle stage, the exoerythrocytic, or liver, stage. here, we show that a small fraction of the inoculum remains in the skin and begins to develop into exoerythrocytic forms that can persist for days. skin exoerythrocytic forms were observed ...201222431651
design, synthesis of 4-aminoquinoline-derived thiazolidines and their antimalarial activity and heme polymerization inhibition studies.the present study describes the synthesis of a series of new 4-aminoquinoline-derived thiazolidines and evaluation of their antimalarial activity against a nf-54 strain of plasmodium falciparum in vitro and n-67 strain of plasmodium yoelii in vivo. among the series, two compounds, 2-(4-chloro-phenyl)-thiazolidine-4-carboxylic acid [2-(7-chloro-quinolin-4-ylamino)-ethyl]-amide hydrochloride (14) and 2-(2,6-dichloro-phenyl)-thiazolidine-4-carboxylic acid [2-(7-chloro-quinolin-4-ylamino)-ethyl]-ami ...201322432870
plasmodium yoelii blood-stage primes macrophage-mediated innate immune response through modulation of toll-like receptor signalling.toll-like receptors (tlrs) signalling is reported to be primed by the infection of human malaria parasite, plasmodium falciparum. however, little is known about the regulation of macrophages tlr signalling by the infection of lethal or non-lethal strain of rodent malaria parasites.201222463100
antiplasmodial activity of novel keto-enamine chalcone-chloroquine based hybrid pharmacophores.a series of novel keto-enamine chalcone-chloroquine based hybrids were synthesized following new methodology developed in our laboratory. the synthesized compounds were screened against chloroquine sensitive strain (3d7) of plasmodium falciparum in an in vitro model. some of the compounds were showing comparable antimalarial activity at par with chloroquine. compounds with significant in vitro antimalarial activity were then evaluated for their in vivo efficacy in swiss mice against plasmodium y ...201222464685
endogenous galectin-3 controls experimental malaria in a species-specific manner.galectins are evolutionarily conserved glycan-binding proteins with pleiotropic roles in innate and adaptive immune responses. galectin-3 has been implicated in several immunological processes as well as in pathogen recognition through specific binding to glycosylated receptors on the surface of host cells or microorganisms. in spite of considerable evidence supporting a role for galectin-3 in host-pathogen interactions, the relevance of this lectin in the regulation of the host defence mechanis ...201222486577
roles of the duffy antigen and glycophorin a in malaria infectionand erythrocyte.we constructed gene knockout mice lacking either the duffy antigen (dfy) or glycophorin a (gpa), major glycoproteins that are expressed on erythrocyte membranes, to examine the role of these proteins in malaria infection and erythrocyte. all of the rodent malarias examined proliferated in the erythrocytes of these knockout mice, indicating that neither the duffy antigen nor gpa has an essential role as a receptor for malaria parasites. duffy antigen knockout mice infected by plasmodium yoelii 17 ...200822504500
sontochin as a guide to the development of drugs against chloroquine-resistant malaria.sontochin was the original chloroquine replacement drug, arising from research by hans andersag 2 years after chloroquine (known as "resochin" at the time) had been shelved due to the mistaken perception that it was too toxic for human use. we were surprised to find that sontochin, i.e., 3-methyl-chloroquine, retains significant activity against chloroquine-resistant strains of plasmodium falciparum in vitro. we prepared derivatives of sontochin, "pharmachins," with alkyl or aryl substituents at ...201222508305
expression of non-tlr pattern recognition receptors in the spleen of balb/c mice infected with plasmodium yoelii and plasmodium chabaudi chabaudi as.the spleen plays a crucial role in the development of immunity to malaria, but the role of pattern recognition receptors (prrs) in splenic effector cells during malaria infection is poorly understood. in the present study, we analysed the expression of selected prrs in splenic effector cells from balb/c mice infected with the lethal and non-lethal plasmodium yoelii strains 17xl and 17x, respectively, and the non-lethal plasmodium chabaudi chabaudi as strain. the results of these experiments show ...201222510838
tlr9 and myd88 are crucial for the development of protective immunity to malaria.effective resolution of malaria infection by avoiding pathogenesis requires regulated pro- to anti-inflammatory responses and the development of protective immunity. tlrs are known to be critical for initiating innate immune responses, but their roles in the regulation of immune responses and development of protective immunity to malaria remain poorly understood. in this study, using wild-type, tlr2(-/-), tlr4(-/-), tlr9(-/-), and myd88(-/-) mice infected with plasmodium yoelii, we show that tlr ...201222516959
vaccine efficacy against malaria by the combination of porcine parvovirus-like particles and vaccinia virus vectors expressing cs of plasmodium.with the aim to develop an efficient and cost-effective approach to control malaria, we have generated porcine parvovirus-like particles (ppv-vlps) carrying the cd8(+) t cell epitope (syvpsaeqi) of the circumsporozoite (cs) protein from plasmodium yoelii fused to the ppv vp2 capsid protein (ppv-pycs), and tested in prime/boost protocols with poxvirus vectors for efficacy in a rodent malaria model. as a proof-of concept, we have characterized the anti-cs cd8(+) t cell response elicited by these h ...201222529915
strong impact of cd4+ foxp3+ regulatory t cells and limited effect of t cell-derived il-10 on pathogen clearance during plasmodium yoelii infection.it is well established that cd4(+)cd25(+)foxp3(+) regulatory t cells (tregs) play a crucial role in the course of different infectious diseases. however, contradictory results have been published regarding to malaria infection. in this study, we report that specific ablation of foxp3(+) tregs in plasmodium yoelii-infected dereg-balb/c mice leads to an increase in t cell activation accompanied by a significant decrease in parasitemia. to better understand how foxp3(+) tregs orchestrate this pheno ...201222544931
efficient control of plasmodium yoelii infection in balb/c and c57bl/6 mice with pre-existing strongyloides ratti infection.about 225 million malaria cases have been reported worldwide in 2009, and one-third of the world's population is infected with parasitic helminths. as helminths and plasmodium are co-endemic, concurrent infections frequently occur. helminths have been shown to modulate the host's immune response; therefore, pre-existing helminth infections may interfere with the efficient immune response to plasmodium. to study the interaction between helminths and plasmodium, we established a murine model of co ...201222554071
apicoap: the first computational model for identifying apicoplast-targeted proteins in multiple species of apicomplexa.most of the parasites of the phylum apicomplexa contain a relict prokaryotic-derived plastid called the apicoplast. this organelle is important not only for the survival of the parasite, but its unique properties make it an ideal drug target. the majority of apicoplast-associated proteins are nuclear encoded and targeted post-translationally to the organellar lumen via a bipartite signaling mechanism that requires an n-terminal signal and transit peptide (tp). attempts to define a consensus moti ...201222574192
evaluation of the immunogenicity and vaccine potential of recombinant plasmodium falciparum merozoite surface protein 8.the c-terminal 19-kda domain of merozoite surface protein 1 (msp1₁₉) is the target of protective antibodies but alone is poorly immunogenic. previously, using the plasmodium yoelii murine model, we fused p. yoelii msp1₁₉ (pymsp1₁₉) with full-length p. yoelii merozoite surface protein 8 (msp8). upon immunization, the msp8-restricted t cell response provided help for the production of high and sustained levels of protective pymsp1₁₉- and pymsp8-specific antibodies. here, we assessed the vaccine po ...201222585960
aryl aryl methyl thio arenes prevent multidrug-resistant malaria in mouse by promoting oxidative stress in parasites.we have synthesized a new series of aryl aryl methyl thio arenes (aamtas) and evaluated antimalarial activity in vitro and in vivo against drug-resistant malaria. these compounds interact with free heme, inhibit hemozoin formation, and prevent plasmodium falciparum growth in vitro in a concentration-dependent manner. these compounds concentration dependently promote oxidative stress in plasmodium falciparum as evident from the generation of intraparasitic oxidants, protein carbonyls, and lipid p ...201222588006
adjuvant-like effect of vaccinia virus 14k protein: a case study with malaria vaccine based on the circumsporozoite protein.development of subunit vaccines for malaria that elicit a strong, long-term memory response is an intensive area of research, with the focus on improving the immunogenicity of a circumsporozoite (cs) protein-based vaccine. in this study, we found that a chimeric protein, formed by fusing vaccinia virus protein 14k (a27) to the cs of plasmodium yoelii, induces strong effector memory cd8(+) t cell responses in addition to high-affinity abs when used as a priming agent in the absence of any adjuvan ...201222615208
novel anti-inflammatory activity of epoxyazadiradione against macrophage migration inhibitory factor: inhibition of tautomerase and proinflammatory activities of macrophage migration inhibitory factor.macrophage migration inhibitory factor (mif) is responsible for proinflammatory reactions in various infectious and non-infectious diseases. we have investigated the mechanism of anti-inflammatory activity of epoxyazadiradione, a limonoid purified from neem (azadirachta indica) fruits, against mif. epoxyazadiradione inhibited the tautomerase activity of mif of both human (humif) and malaria parasites (plasmodium falciparum (pfmif) and plasmodium yoelii (pymif)) non-competitively in a reversible ...201222645149
plasmodium yoelii blood-stage antigens newly identified by immunoaffinity using purified igg antibodies from malaria-resistant mice.as the search for an effective human malaria vaccine continues, understanding immune responses to plasmodium in rodent models is perhaps the key to unlocking new vaccine strategies. the recruitment of parasite-specific antibodies is an important component of natural immunity against infection in blood-stage malaria. here, we describe the use of sera from naturally surviving icr mice after infection with lethal doses of plasmodium yoelii yoelii 17xl to identify highly immunogenic blood-stage anti ...201222658767
qsar, docking and admet studies of artemisinin derivatives for antimalarial activity targeting plasmepsin ii, a hemoglobin-degrading enzyme from p. falciparum.this work presents the development of quantitative structure activity relationship (qsar) model to predict the antimalarial activity of artemisinin derivatives. the structures of the molecules are represented by chemical descriptors that encode topological, geometric, and electronic structure features. screening through qsar model suggested that compounds a24, a24a, a53, a54, a62 and a64 possess significant antimalarial activity. linear model is developed by the multiple linear regression method ...201222670592
supplement of l-arg improves protective immunity during early-stage plasmodium yoelii 17xl infection.l-arginine (l-arg), the precursor of nitric oxide (no), plays multiple important roles in nutrient metabolism and immune regulation. l-arg supplement serves as a potential adjunctive therapy for severe malaria, because it improves no bioavailability and reverses endothelial dysfunction in severe malaria patients. in this study, we investigated the effect of dietary l-arg supplement on host immune responses during subsequent malaria infection using the plasmodium yoelii 17xl - balb/c mouse model. ...201322709481
in vitro human cell-free expression system for synthesis of malaria proteins.in this study, we performed cell-free expression of plasmodium proteins using the in vitro human cell-free protein expression systems for dna and mrna. malaria rhoptry genes (pfc14_0344, pfc0120w, py01759, py00763, py07482, and py04666) and a maurer's cleft gene (pfa0680c) identified from proteome analysis studies were cloned into the pt7cfe1-chis expression vector. following a coupled transcription-translation procedure, expressed proteins were analyzed by his-tag staining and by western blotti ...201222782471
the species specificity of immunity generated by live whole organism immunisation with erythrocytic and pre-erythrocytic stages of rodent malaria parasites and implications for vaccine development.a promising strategy for the development of a malaria vaccine involves the use of attenuated whole parasites, as these present a greater repertoire of antigens to the immune system than subunit vaccines. the complexity of the malaria parasite's life cycle offers multiple stages on which to base an attenuated whole organism vaccine. an important consideration in the design and employment of such vaccines is the diversity of the parasites that are infective to humans. the most valuable vaccine wou ...201222846785
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