| 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 ... | 2010 | 20951034 |
| 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 ... | 2010 | 20958156 |
| 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 ... | 2010 | 21039472 |
| 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 ... | 2010 | 21060850 |
| 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 ... | 2010 | 21086719 |
| 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 ... | 2010 | 21122144 |
| 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. | 2010 | 21126362 |
| 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 ... | 2010 | 21131051 |
| 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 ... | 2010 | 21139212 |
| 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 ... | 2010 | 21153838 |
| 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. | 2010 | 21159170 |
| 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 ... | 2010 | 21168413 |
| 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 ... | 2011 | 21226727 |
| 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 ... | 2011 | 21245909 |
| 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 ... | 2011 | 21248692 |
| 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 ... | 2011 | 21282967 |
| 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 ... | 2011 | 21283619 |
| 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 ... | 2010 | 21299648 |
| 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. | 2011 | 21323481 |
| 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 ... | 2011 | 21354479 |
| 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 ... | 2011 | 21361304 |
| 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 ... | 2011 | 21366672 |
| 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 ... | 2011 | 21379566 |
| [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 ... | 2010 | 21391181 |
| 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 ... | 2011 | 21410955 |
| 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 ... | 2011 | 21469097 |
| 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 ... | 2011 | 21482683 |
| daily plasmodium yoelii infective mosquito bites do not generate protection or suppress previous immunity against the liver stage. | abstract: | 2011 | 21501513 |
| parasitostatic effect of maslinic acid. ii. survival increase and immune protection in lethal plasmodium yoelii-infected mice. | abstract: | 2011 | 21518429 |
| 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 ... | 2011 | 21541755 |
| 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 ... | 2011 | 21619927 |
| 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 ... | 2011 | 21625465 |
| 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 ... | 2011 | 21673450 |
| 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 ... | 2011 | 21813775 |
| 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 ... | 2011 | 21807905 |
| 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 ... | 2011 | 21807053 |
| 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 ... | 2011 | 21777589 |
| 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. | 2011 | 21771471 |
| 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 ... | 2011 | 21756423 |
| [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. | 2011 | 21823319 |
| 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 ... | 2011 | 21819513 |
| 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 ... | 2011 | 21690382 |
| etiopathogenesis of burkitt's lymphoma: a lesson from a bl-like in cd1 mouse immune to plasmodium yoelii yoelii. | abstract: | 2011 | 21740585 |
| 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 ... | 2010 | 21731168 |
| 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 ... | 2011 | 21881756 |
| 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. | 2011 | 22053595 |
| 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 ... | 2011 | 21909259 |
| 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 ... | 2011 | 21856338 |
| 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 ... | 2011 | 21929749 |
| 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 ... | 2011 | 22096610 |
| 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 ... | 2011 | 22046311 |
| 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 ... | 2011 | 22017443 |
| 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 ... | 2011 | 22179318 |
| 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 ... | 2011 | 21915626 |
| 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 ... | 2011 | 22205939 |
| 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 ... | 2011 | 22015474 |
| 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 ... | 2011 | 22119928 |
| [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. | 2011 | 21972595 |
| 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 ... | 2011 | 21876036 |
| 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 ... | 2011 | 21939717 |
| 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 ... | 2011 | 21945268 |
| 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 ... | 2011 | 22170105 |
| 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 ... | 2011 | 21998455 |
| 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 ... | 2011 | 21907206 |
| 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 ... | 2012 | 22242171 |
| 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 ... | 2012 | 22216834 |
| 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 ... | 2011 | 22294247 |
| 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 ... | 2011 | 22215999 |
| synthesis and insight into the structure-activity relationships of chalcones as antimalarial agents. | licochalcone a (i), isolated from the roots of chinese licorice, is the most promising antimalarial compound reported so far. in continuation of our drug discovery program, we isolated two similar chalcones, medicagenin (ii) and munchiwarin (iii), from crotalaria medicagenia , which exhibited antimalarial activity against plasmodium falciparum . a library of 88 chalcones were synthesized and evaluated for their in vitro antimalarial activity. among these, 67, 68, 74, 77, and 78 exhibited good in ... | 2012 | 23270565 |
| capacity of mosquitoes to transmit malaria depends on larval environment. | adult traits of holometabolous insects such as reproduction and survival can be shaped by conditions experienced during larval development. these "carry-over" effects influence not only individual life history and fitness, but can also impact interactions between insect hosts and parasites. despite this, the implications of larval conditions for the transmission of human, wildlife and plant diseases that are vectored by insects remain poorly understood. | 2014 | 25496502 |
| immunization with the maebl m2 domain protects against lethal plasmodium yoelii infection. | malaria remains a world-threatening disease largely because of the lack of a long-lasting and fully effective vaccine. maebl is a type 1 transmembrane molecule with a chimeric cysteine-rich ectodomain homologous to regions of the duffy binding-like erythrocyte binding protein and apical membrane antigen 1 (ama1) antigens. although maebl does not appear to be essential for the survival of blood-stage forms, ectodomains m1 and m2, homologous to ama1, seem to be involved in parasite attachment to e ... | 2015 | 26169268 |
| assessment of antibody-dependent respiratory burst activity from mouse neutrophils on plasmodium yoelii malaria challenge outcome. | new tools are required to expedite the development of an effective vaccine against the blood-stage infection with the human malaria parasite plasmodium falciparum. this work describes the assessment of the adrb assay in a mouse model, characterizing the functional interaction between antimalarial serum antibodies and fcrs upon neutrophils. we describe a reproducible, antigen-specific assay, dependent on functional fcr signaling, and show that adrb activity is induced equally by igg1 and igg2a is ... | 2013 | 24163420 |
| a chimeric plasmodium falciparum merozoite surface protein vaccine induces high titers of parasite growth inhibitory antibodies. | the c-terminal 19-kda domain of plasmodium falciparum merozoite surface protein 1 (pfmsp119) is an established target of protective antibodies. however, clinical trials of pfmsp142, a leading blood-stage vaccine candidate which contains the protective epitopes of pfmsp119, revealed suboptimal immunogenicity and efficacy. based on proof-of-concept studies in the plasmodium yoelii murine model, we produced a chimeric vaccine antigen containing recombinant pfmsp119 (rpfmsp119) fused to the n termin ... | 2013 | 23897613 |
| 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 ... | 2012 | 22585960 |
| experimental immunization based on plasmodium antigens isolated by antibody affinity. | vaccines blocking malaria parasites in the blood-stage diminish mortality and morbidity caused by the disease. here, we isolated antigens from total parasite proteins by antibody affinity chromatography to test an immunization against lethal malaria infection in a murine model. we used the sera of malaria self-resistant icr mice to lethal plasmodium yoelii yoelii 17xl for purification of their iggs which were subsequently employed to isolate blood-stage parasite antigens that were inoculated to ... | 2015 | 26539558 |
| the utility of plasmodium berghei as a rodent model for anti-merozoite malaria vaccine assessment. | rodent malaria species plasmodium yoelii and p. chabaudi have been widely used to validate vaccine approaches targeting blood-stage merozoite antigens. however, increasing data suggest the p. berghei rodent malaria may be able to circumvent vaccine-induced anti-merozoite responses. here we confirm a failure to protect against p. berghei, despite successful antibody induction against leading merozoite antigens using protein-in-adjuvant or viral vectored vaccine delivery. no subunit vaccine approa ... | 0 | 23609325 |
| an overview of malaria transmission from the perspective of amazon anopheles vectors. | in the americas, areas with a high risk of malaria transmission are mainly located in the amazon forest, which extends across nine countries. one keystone step to understanding the plasmodium life cycle in anopheles species from the amazon region is to obtain experimentally infected mosquito vectors. several attempts to colonise anopheles species have been conducted, but with only short-lived success or no success at all. in this review, we review the literature on malaria transmission from the ... | 2015 | 25742262 |
| ambient temperature and dietary supplementation interact to shape mosquito vector competence for malaria. | the extent to which environmental factors influence the ability of anopheles mosquitoes to transmit malaria parasites remains poorly explored. environmental variation, such as change in ambient temperature, will not necessarily influence the rates of host and parasite processes equivalently, potentially resulting in complex effects on infection outcomes. as proof of principle, we used anopheles stephensi and the rodent malaria parasite, plasmodium yoelii, to examine the effects of a range of con ... | 2014 | 24911425 |
| susceptibility to plasmodium liver stage infection is altered by hepatocyte polyploidy. | plasmodium parasites infect hepatocytes of their mammalian hosts and undergo obligate liver stage development. the specific host cell attributes that are important for liver infection remain largely unknown. several host signalling pathways are perturbed in infected hepatocytes, some of which are important in the generation of hepatocyte polyploidy. to test the functional consequence of polyploidy on liver infection, we infected hepatocytes with the rodent malaria parasite plasmodium yoelii both ... | 2014 | 24612025 |
| modulation of anopheles stephensi gene expression by nitroquine, an antimalarial drug against plasmodium yoelii infection in the mosquito. | antimalarial drugs may impact mosquito's defense against plasmodium parasites. our previous study showed nitroquine significantly reduced infection of anopheles stephensi by plasmodium yoelii, but the underlying mechanism remains unclear. in order to understand how transmission capacity of an. stephensi was affected by nitroquine, we explored the transcriptome of adult females after different treatments, examined changes in gene expression profiles, and identified transcripts affected by the dru ... | 2014 | 24586804 |
| model for in vivo assessment of humoral protection against malaria sporozoite challenge by passive transfer of monoclonal antibodies and immune serum. | evidence from clinical trials of malaria vaccine candidates suggests that both cell-mediated and humoral immunity to pre-erythrocytic parasite stages can provide protection against infection. novel pre-erythrocytic antibody (ab) targets could be key to improving vaccine formulations, which are currently based on targeting antigens such as the circumsporozoite protein (csp). however, methods to assess the effects of sporozoite-specific abs on pre-erythrocytic infection in vivo remain underdevelop ... | 2013 | 24478094 |
| enzymes involved in plastid-targeted phosphatidic acid synthesis are essential for plasmodium yoelii liver-stage development. | malaria parasites scavenge nutrients from their host but also harbour enzymatic pathways for de novo macromolecule synthesis. one such pathway is apicoplast-targeted type ii fatty acid synthesis, which is essential for late liver-stage development in rodent malaria. it is likely that fatty acids synthesized in the apicoplast are ultimately incorporated into membrane phospholipids necessary for exoerythrocytic merozoite formation. we hypothesized that these synthesized fatty acids are being utili ... | 2014 | 24330260 |
| hla class ii (dr0401) molecules induce foxp3+ regulatory t cell suppression of b cells in plasmodium yoelii strain 17xnl malaria. | unlike human malaria parasites that induce persistent infection, some rodent malaria parasites, like plasmodium yoelii strain 17xnl (py17xnl), induce a transient (self-curing) malaria infection. cooperation between cd4 t cells and b cells to produce antibodies is thought to be critical for clearance of py17xnl parasites from the blood, with major histocompatibility complex (mhc) class ii molecules being required for activation of cd4 t cells. in order to better understand the correspondence betw ... | 2013 | 24166949 |
| larval nutrition differentially affects adult fitness and plasmodium development in the malaria vectors anopheles gambiae and anopheles stephensi. | mosquito fitness is determined largely by body size and nutritional reserves. plasmodium infections in the mosquito and resultant transmission of malaria parasites might be compromised by the vector's nutritional status. we studied the effects of nutritional stress and malaria parasite infections on transmission fitness of anopheles mosquitoes. | 2013 | 24326030 |
| hypoxia promotes liver-stage malaria infection in primary human hepatocytes in vitro. | homeostasis of mammalian cell function strictly depends on balancing oxygen exposure to maintain energy metabolism without producing excessive reactive oxygen species. in vivo, cells in different tissues are exposed to a wide range of oxygen concentrations, and yet in vitro models almost exclusively expose cultured cells to higher, atmospheric oxygen levels. existing models of liver-stage malaria that utilize primary human hepatocytes typically exhibit low in vitro infection efficiencies, possib ... | 2013 | 24291761 |
| short-lived effector cd8 t cells induced by genetically attenuated malaria parasite vaccination express cd11c. | vaccination with a single dose of genetically attenuated malaria parasites can induce sterile protection against sporozoite challenge in the rodent plasmodium yoelii model. protection is dependent on cd8(+) t cells, involves perforin and gamma interferon (ifn-γ), and is correlated with the expansion of effector memory cd8(+) t cells in the liver. here, we have further characterized vaccine-induced changes in the cd8(+) t cell phenotype and demonstrated significant upregulation of cd11c on cd3(+) ... | 2013 | 23980113 |
| in vivo cd8+ t cell dynamics in the liver of plasmodium yoelii immunized and infected mice. | plasmodium falciparum malaria remains one of the most serious health problems globally and a protective malaria vaccine is desperately needed. vaccination with attenuated parasites elicits multiple cellular effector mechanisms that lead to plasmodium liver stage elimination. while granule-mediated cytotoxicity requires contact between cd8+ effector t cells and infected hepatocytes, cytokine secretion should allow parasite killing over longer distances. to better understand the mechanism of paras ... | 2013 | 23967119 |
| malaria parasite liver stages render host hepatocytes susceptible to mitochondria-initiated apoptosis. | intracellular eukaryotic parasites and their host cells constitute complex, coevolved cellular interaction systems that frequently cause disease. among them, plasmodium parasites cause a significant health burden in humans, killing up to one million people annually. to succeed in the mammalian host after transmission by mosquitoes, plasmodium parasites must complete intracellular replication within hepatocytes and then release new infectious forms into the blood. using plasmodium yoelii rodent m ... | 2013 | 23928701 |
| 'manipulation' without the parasite: altered feeding behaviour of mosquitoes is not dependent on infection with malaria parasites. | previous studies have suggested that plasmodium parasites can manipulate mosquito feeding behaviours such as probing, persistence and engorgement rate in order to enhance transmission success. here, we broaden analysis of this 'manipulation phenotype' to consider proximate foraging behaviours, including responsiveness to host odours and host location. using anopheles stephensi and plasmodium yoelii as a model system, we demonstrate that mosquitoes with early stage infections (i.e. non-infectious ... | 2013 | 23698008 |
| a member of the cpw-wpc protein family is expressed in and localized to the surface of developing ookinetes. | despite the development of malaria control programs, billions of people are still at risk for this infectious disease. recently, the idea of the transmission-blocking vaccine, which works by interrupting the infection of mosquitoes by parasites, has gained attention as a promising strategy for malaria control and eradication. to date, a limited number of surface proteins have been identified in mosquito-stage parasites and investigated as potential targets for transmission-blocking vaccines. the ... | 2013 | 23587146 |
| quantitative bioluminescent imaging of pre-erythrocytic malaria parasite infection using luciferase-expressing plasmodium yoelii. | the liver stages of plasmodium parasites are important targets for the development of anti-malarial vaccine candidates and chemoprophylaxis approaches that aim to prevent clinical infection. analyzing the impact of interventions on liver stages in the murine malaria model system plasmodium yoelii has been cumbersome and requires terminal procedures. in vivo imaging of bioluminescent parasites has previously been shown to be an effective and non-invasive alternative to monitoring liver stage burd ... | 2013 | 23593316 |
| nonobese diabetic (nod) mice lack a protective b-cell response against the "nonlethal" plasmodium yoelii 17xnl malaria protozoan. | background. plasmodium yoelii 17xnl is a nonlethal malaria strain in mice of different genetic backgrounds including the c57bl/6 mice (i-a(b)/i-e(null)) used in this study as a control strain. we have compared the trends of blood stage infection with the nonlethal murine strain of p. yoelii 17xnl malaria protozoan in immunocompetent nonobese diabetic (nod) mice prone to type 1 diabetes (t1d) and c57bl/6 mice (control mice) that are not prone to t1d and self-cure the p. yoelii 17xnl infection. pr ... | 2016 | 28074170 |
| plasmodium yoelii nigeriensis (n67) is a robust animal model to study malaria transmission by south american anopheline mosquitoes. | malaria is endemic in the american continent and the amazonian rainforest is the region with the highest risk of transmission. however, the lack of suitable experimental models to infect malaria vectors from the americas has limited the progress to understand the biology of transmission in this region. anopheles aquasalis, a major vector in coastal areas of south america, was found to be highly refractory to infection with two strains of plasmodium falciparum (nf54 and 7g8) and with plasmodium b ... | 2016 | 27911924 |
| effects of transmission-blocking vaccines simultaneously targeting pre- and post-fertilization antigens in the rodent malaria parasite plasmodium yoelii. | transmission-blocking vaccine (tbv) is a promising strategy for interrupting the malaria transmission cycle. current tbv candidates include both pre- and post-fertilization antigens expressed during sexual development of the malaria parasites. | 2016 | 27502144 |
| in vitro analysis of the interaction between atovaquone and proguanil against liver stage malaria parasites. | the interaction between atovaquone and proguanil has never been studied against liver stage malaria, which is the main target of this drug combination when used for chemoprevention. using human hepatocytes lacking cytochrome p450 activity, and thus avoiding proguanil metabolizing into potent cycloguanil, we show in vitro that the atovaquone-proguanil combination synergistically inhibits the growth of rodent plasmodium yoelii parasites. these results provide a pharmacological basis for the high e ... | 2016 | 26926628 |
| a plasmodium promiscuous t cell epitope delivered within the ad5 hexon protein enhances the protective efficacy of a protein based malaria vaccine. | a malaria vaccine is a public health priority. in order to produce an effective vaccine, a multistage approach targeting both the blood and the liver stage infection is desirable. the vaccine candidates also need to induce balanced immune responses including antibodies, cd4+ and cd8+ t cells. protein-based subunit vaccines like rts,s are able to induce strong antibody response but poor cellular reactivity. adenoviral vectors have been effective inducing protective cd8+ t cell responses in severa ... | 2016 | 27128437 |
| co-administration of α-galcer analog and tlr4 agonist induces robust cd8(+) t-cell responses to pycs protein and wt-1 antigen and activates memory-like effector nkt cells. | in the present study, the combined adjuvant effect of 7dw8-5, a potent α-galcer-analog, and monophosphoryl lipid a (mpla), a tlr4 agonist, on the induction of vaccine-induced cd8(+) t-cell responses and protective immunity was evaluated. mice were immunized with peptides corresponding to the cd8(+) t-cell epitopes of a malaria antigen, a circumsporozoite protein of plasmodium yoelii, and a tumor antigen, a wilms tumor antigen-1 (wt-1), together with 7dw8-5 and mpla, as an adjuvant. these immuniz ... | 2016 | 27132023 |
| defining rules of cd8(+) t cell expansion against pre-erythrocytic plasmodium antigens in sporozoite-immunized mice. | whole plasmodium sporozoites serve as both experimental tools and potentially as deployable vaccines in the fight against malaria infection. live sporozoites infect hepatocytes and induce a diverse repertoire of cd8(+) t cell responses, some of which are capable of killing plasmodium-infected hepatocytes. previous studies in plasmodium yoelii-immunized balb/c mice showed that some cd8(+) t cell responses expanded with repeated parasite exposure, whereas other responses did not. | 2016 | 27113469 |
| a plasmodium yoelii mei2-like rna binding protein is essential for completion of liver stage schizogony. | plasmodium parasites employ posttranscriptional regulatory mechanisms as their life cycle transitions between host cell invasion and replication within both the mosquito vector and mammalian host. rna binding proteins (rbps) provide one mechanism for modulation of rna function. to explore the role of plasmodium rbps during parasite replication, we searched for rbps that might play a role during liver stage development, the parasite stage that exhibits the most extensive growth and replication. w ... | 2016 | 26883588 |
| enhanced transmission of malaria parasites to mosquitoes in a murine model of type 2 diabetes. | more than half of the world's population is at risk of malaria and simultaneously, many malaria-endemic regions are facing dramatic increases in the prevalence of type 2 diabetes. studies in murine malaria models have examined the impact of malaria infection on type 2 diabetes pathology, it remains unclear how this chronic metabolic disorder impacts the transmission of malaria. in this report, the ability type 2 diabetic rodents infected with malaria to transmit parasites to anopheles stephensi ... | 2016 | 27102766 |