Publications
66 results found
Blagborough AM, Musiychuk K, Bi H, et al., 2016, Transmission blocking potency and immunogenicity of a plant-produced Pvs25-based subunit vaccine against Plasmodium vivax, Vaccine, Vol: 34, Pages: 3252-3259, ISSN: 1873-2518
Malaria transmission blocking (TB) vaccines (TBVs) directed against proteins expressed on the sexual stages of Plasmodium parasites are a potentially effective means to reduce transmission. Antibodies induced by TBVs block parasite development in the mosquito, and thus inhibit transmission to further human hosts. The ookinete surface protein P25 is a primary target for TBV development. Recently, transient expression in plants using hybrid viral vectors has demonstrated potential as a strategy for cost-effective and scalable production of recombinant vaccines. Using a plant virus-based expression system, we produced recombinant P25 protein of Plasmodium vivax (Pvs25) in Nicotiana benthamiana fused to a modified lichenase carrier protein. This candidate vaccine, Pvs25-FhCMB, was purified, characterized and evaluated for immunogenicity and efficacy using multiple adjuvants in a transgenic rodent model. An in vivo TB effect of up to a 65% reduction in intensity and 54% reduction in prevalence was observed using Abisco-100 adjuvant. The ability of this immunogen to induce a TB response was additionally combined with heterologous prime-boost vaccination with viral vectors expressing Pvs25. Significant blockade was observed when combining both platforms, achieving a 74% and 68% reduction in intensity and prevalence, respectively. This observation was confirmed by direct membrane feeding on field P. vivax samples, resulting in reductions in intensity/prevalence of 85.3% and 25.5%. These data demonstrate the potential of this vaccine candidate and support the feasibility of expressing Plasmodium antigens in a plant-based system for the production of TBVs, while demonstrating the potential advantages of combining multiple vaccine delivery systems to maximize efficacy.
Bauza K, Atcheson E, Malinauskas T, et al., 2015, Tailoring a combination preerythrocytic malaria vaccine, Infection and Immunity, Vol: 84, Pages: 622-634, ISSN: 1098-5522
The leading malaria vaccine candidate, RTS,S, based on the Plasmodium falciparum circumsporozoite protein (CSP), will likely be the first publicly adopted malaria vaccine. However, this and other subunit vaccines, such as virus-vectored thrombospondin-related adhesive protein (TRAP), provide only intermediate to low levels of protection. In this study, the Plasmodium berghei homologues of antigens CSP and TRAP are combined. TRAP is delivered using adenovirus- and vaccinia virus-based vectors in a prime-boost regime. Initially, CSP is also delivered using these viral vectors; however, a reduction of anti-CSP antibodies is seen when combined with virus-vectored TRAP, and the combination is no more protective than either subunit vaccine alone. Using an adenovirus-CSP prime, protein-CSP boost regime, however, increases anti-CSP antibody titers by an order of magnitude, which is maintained when combined with virus-vectored TRAP. This combination regime using protein CSP provided 100% protection in C57BL/6 mice compared to no protection using virus-vectored TRAP alone and 40% protection using adenovirus-CSP prime and protein-CSP boost alone. This suggests that a combination of CSP and TRAP subunit vaccines could enhance protection against malaria.
Ortega-Prieto AM, Wai SN, Large EM, et al., 2015, Microfluidic liver cultures as preclinical tool for the study of hepatitis B and C virus as well as malaria, AASLD, Publisher: WILEY-BLACKWELL, Pages: 1383A-1383A, ISSN: 0270-9139
Sherrard-Smith E, Upton L, Zakutansky S, et al., 2015, THE COMBINED IMPACT OF TRANSMISSION-BLOCKING DRUGS AND RTS, S VACCINES IS SYNERGISTIC?, Publisher: AMER SOC TROP MED & HYGIENE, Pages: 503-503, ISSN: 0002-9637
Baragana B, Hallyburton I, Lee MCS, et al., 2015, A novel multiple-stage antimalarial agent that inhibits protein synthesis, Nature, Vol: 522, Pages: 315-320, ISSN: 0028-0836
There is an urgent need for new drugs to treat malaria, with broad therapeutic potential and novel modes of action, to widen the scope of treatment and to overcome emerging drug resistance. Here we describe the discovery of DDD107498, a compound with a potent and novel spectrum of antimalarial activity against multiple life-cycle stages of the Plasmodium parasite, with good pharmacokinetic properties and an acceptable safety profile. DDD107498 demonstrates potential to address a variety of clinical needs, including single-dose treatment, transmission blocking and chemoprotection. DDD107498 was developed from a screening programme against blood-stage malaria parasites; its molecular target has been identified as translation elongation factor 2 (eEF2), which is responsible for the GTP-dependent translocation of the ribosome along messenger RNA, and is essential for protein synthesis. This discovery of eEF2 as a viable antimalarial drug target opens up new possibilities for drug discovery.
Kapulu MC, Da DF, Miura K, et al., 2015, Comparative Assessment of Transmission-Blocking Vaccine Candidates against Plasmodium falciparum, Scientific Reports, Vol: 5, ISSN: 2045-2322
Malaria transmission-blocking vaccines (TBVs) target the development of Plasmodium parasiteswithin the mosquito, with the aim of preventing malaria transmission from one infected individual toanother. Different vaccine platforms, mainly protein-in-adjuvant formulations delivering the leadingcandidate antigens, have been developed independently and have reported varied transmissionblockingactivities (TBA). Here, recombinant chimpanzee adenovirus 63, ChAd63, and modifiedvaccinia virus Ankara, MVA, expressing AgAPN1, Pfs230-C, Pfs25, and Pfs48/45 were generated.Antibody responses primed individually against all antigens by ChAd63 immunization in BALB/cmice were boosted by the administration of MVA expressing the same antigen. These antibodiesexhibited a hierarchy of inhibitory activity against the NF54 laboratory strain of P. falciparum inAnopheles stephensi mosquitoes using the standard membrane feeding assay (SMFA), with antiPfs230-Cand anti-Pfs25 antibodies giving complete blockade. The observed rank order of inhibitionwas replicated against P. falciparum African field isolates in A. gambiae in direct membrane feedingassays (DMFA). TBA achieved was IgG concentration dependent. This study provides the first headto-headcomparative analysis of leading antigens using two different parasite sources in two differentvector species, and can be used to guide selection of TBVs for future clinical development using theviral-vectored delivery platform.
Marques SR, Ramakrishnan C, Carzaniga R, et al., 2015, An essential role of the basal body protein SAS-6 in <i>Plasmodium</i> male gamete development and malaria transmission, CELLULAR MICROBIOLOGY, Vol: 17, Pages: 191-206, ISSN: 1462-5814
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- Citations: 25
Sala KA, Nishiura H, Upton LM, et al., 2015, The Plasmodium berghei sexual stage antigen PSOP12 induces anti-malarial transmission blocking immunity both in vivo and in vitro, Vaccine, Vol: 33, Pages: 437-445, ISSN: 1873-2518
Anti-malarial transmission-blocking vaccines (TBVs) aim to inhibit the transmission of Plasmodium from humans to mosquitoes by targeting the sexual/ookinete stages of the parasite. Successful use of such interventions will subsequently result in reduced cases of malarial infection within a human population, leading to local elimination. There are currently only five lead TBV candidates under examination. There is a consequent need to identify novel antigens to allow the formulation of new potent TBVs. Here we describe the design and evaluation of a potential TBV (BDES-PbPSOP12) targeting Plasmodium berghei PSOP12 based on the baculovirus dual expression system (BDES), enabling expression of antigens on the surface of viral particles and within infected mammalian cells. In silico studies have previously suggested that PSOP12 (Putative Secreted Ookinete Protein 12) is expressed within the sexual stages of the parasite (gametocytes, gametes and ookinetes), and is a member of the previously characterized 6-Cys family of plasmodial proteins. We demonstrate that PSOP12 is expressed within the sexual/ookinete forms of the parasite, and that sera obtained from mice immunized with BDES-PbPSOP12 can recognize the surface of the male and female gametes, and the ookinete stages of the parasite. Immunization of mice with BDES-PbPSOP12 confers modest but significant transmission-blocking activity in vivo by active immunization (53.1% reduction in oocyst intensity, 10.9% reduction in oocyst prevalence). Further assessment of transmission-blocking potency ex vivo shows a dose-dependent response, with up to a 76.4% reduction in intensity and a 47.2% reduction in prevalence observed. Our data indicates that PSOP12 in Plasmodium spp. could be a potential new TBV target candidate, and that further experimentation to examine the protein within human malaria parasites would be logical.
Upton LM, Brock PM, Churcher TS, et al., 2015, Lead Clinical and Preclinical Antimalarial Drugs Can Significantly Reduce Sporozoite Transmission to Vertebrate Populations, ANTIMICROBIAL AGENTS AND CHEMOTHERAPY, Vol: 59, Pages: 490-497, ISSN: 0066-4804
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- Citations: 19
Da DF, Churcher TS, Yerbanga RS, et al., 2014, Experimental study of the relationship between Plasmodium gametocyte density and infection success in mosquitoes; implications for the evaluation of malaria transmission-reducing interventions, Experimental Parasitology, Vol: 149, Pages: 74-83, ISSN: 1090-2449
The evaluation of transmission reducing interventions (TRI) to control malaria widely uses membrane feeding assays. In such assays, the intensity of Plasmodium infection in the vector might affect the measured efficacy of the candidates to block transmission. Gametocyte density in the host blood is a determinant of the infection success in the mosquito, however, uncertain estimates of parasite densities and intrinsic characteristics of the infected blood can induce variability. To reduce this variation, a feasible method is to dilute infectious blood samples. We describe the effect of diluting samples of Plasmodium-containing blood samples to allow accurate relative measures of gametocyte densities and their impact on mosquito infectivity and TRI efficacy. Natural Plasmodium falciparum samples were diluted to generate a wide range of parasite densities, and fed to Anopheles coluzzii mosquitoes. This was compared with parallel dilutions conducted on Plasmodium berghei infections. We examined how blood dilution influences the observed blocking activity of anti-Pbs28 monoclonal antibody using the P. berghei/Anopheles stephensi system.In the natural species combination P. falciparum/An. coluzzii, blood dilution using heat-inactivated, infected blood as diluents, revealed positive near linear relationships, between gametocyte densities and oocyst loads in the range tested. A similar relationship was observed in the P. berghei/An. stephensi system when using a similar dilution method. In contrast, diluting infected mice blood with fresh uninfected blood dramatically increases the infectiousness. This suggests that highly infected mice blood contains inhibitory factors or reduced blood moieties, which impede infection and may in turn, lead to misinterpretation when comparing individual TRI evaluation assays. In the lab system, the transmission blocking activity of an antibody specific for Pbs28 was confirmed to be density-dependent. This highlights the need to carefully in
Mizutani M, Iyori M, Blagborough AM, et al., 2014, Baculovirus-Vectored Multistage <i>Plasmodium vivax</i> Vaccine Induces Both Protective and Transmission-Blocking Immunities against Transgenic Rodent Malaria Parasites, INFECTION AND IMMUNITY, Vol: 82, Pages: 4348-4357, ISSN: 0019-9567
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- Citations: 30
Blagborough AM, Churcher T, Upton LM, et al., 2013, TRANSMISSION-BLOCKING INTERVENTIONS ELIMINATE MALARIA FROM LABORATORY POPULATIONS, PATHOGENS AND GLOBAL HEALTH, Vol: 107, Pages: 456-456, ISSN: 2047-7724
Churcher T, Basanez M-G, Blagborough A, et al., 2013, IS PARASITE DENSITY IMPORTANT IN MALARIA TRANSMISSION?, PATHOGENS AND GLOBAL HEALTH, Vol: 107, Pages: 450-451, ISSN: 2047-7724
Ewer KJ, O'Hara GA, Duncan CJA, et al., 2013, Protective CD8(+) T-cell immunity to human malaria induced by chimpanzee adenovirus-MVA immunisation, Nature Communications, Vol: 4, ISSN: 2041-1723
Induction of antigen-specific CD8 þ T cells offers the prospect of immunization against manyinfectious diseases, but no subunit vaccine has induced CD8 þ T cells that correlate withefficacy in humans. Here we demonstrate that a replication-deficient chimpanzee adenovirusvector followed by a modified vaccinia virus Ankara booster induces exceptionally high frequencyT-cell responses (median 42400 SFC/106 peripheral blood mononuclear cells) tothe liver-stage Plasmodium falciparum malaria antigen ME-TRAP. It induces sterile protectiveefficacy against heterologous strain sporozoites in three vaccinees (3/14, 21%), and delaystime to patency through substantial reduction of liver-stage parasite burden in five more(5/14, 36%), P ¼ 0.008 compared with controls. The frequency of monofunctional interferon-g-producingCD8 þ T cells, but not antibodies, correlates with sterile protectionand delay in time to patency (Pcorrected ¼ 0.005). Vaccine-induced CD8 þ T cells provideprotection against human malaria, suggesting that a major limitation of previous vaccinationapproaches has been the insufficient magnitude of induced T cells.
Blagborough AM, Churcher TS, Upton LM, et al., 2013, Transmission-blocking interventions eliminate malaria from laboratory populations, Nature Communications, Vol: 4, ISSN: 2041-1723
Transmission-blocking interventions aim to reduce the prevalence of infection in endemic communities by targeting Plasmodium within the insect host. Although many studies have reported the successful reduction of infection in the mosquito vector, direct evidence that there is an onward reduction in infection in the vertebrate host is lacking. Here we report the first experiments using a population, transmission-based study of Plasmodium berghei in Anopheles stephensi to assess the impact of a transmission-blocking drug upon both insect and host populations over multiple transmission cycles. We demonstrate that the selected transmission-blocking intervention, which inhibits transmission from vertebrate to insect by only 32%, reduces the basic reproduction number of the parasite by 20%, and in our model system can eliminate Plasmodium from mosquito and mouse populations at low transmission intensities. These findings clearly demonstrate that use of transmission-blocking interventions alone can eliminate Plasmodium from a vertebrate population, and have significant implications for the future design and implementation of transmission-blocking interventions within the field.
Ramakrishnan C, Delves MJ, Lal K, et al., 2013, Laboratory maintenance of rodent malaria parasites., Malaria: Methods and Protocols, Editors: Ménard, Pages: 51-72
Blagborough AM, Delves MJ, Ramakrishnan C, et al., 2013, Assessing Transmission Blockade in Plasmodium spp., Malaria: Methods and Protocols, Editors: Ménard, Pages: 577-600
Wass MN, Stanway R, Blagborough AM, et al., 2012, Proteomic analysis of Plasmodium in the mosquito: progress and pitfalls, Parasitology, Vol: 139, Pages: 1131-1145, ISSN: 1469-8161
Here we discuss proteomic analyses of whole cell preparations of the mosquito stages of malaria parasite development (i.e.gametocytes, microgamete, ookinete, oocyst and sporozoite) of Plasmodium berghei. We also include critiques of theproteomes of two cell fractions from the purified ookinete, namely the micronemes and cell surface. Whereas we summarisekey biological interpretations of the data, we also try to identify key methodological constraints we have met, only some ofwhich we were able to resolve. Recognising the need to translate the potential of current genome sequencing into functionalunderstanding, we report our efforts to develop more powerful combinations of methods for the in silico prediction ofprotein function and location. We have applied this analysis to the proteome of the male gamete, a cell whose very simplestructural organisation facilitated interpretation of data. Some of the in silico predictions made have now been supported byongoing protein tagging and genetic knockout studies. We hope this discussion may assist future studies.
Sinden RE, Blagborough AM, Churcher T, et al., 2012, The design and interpretation of laboratory assays measuring mosquito transmission of Plasmodium., Trends in Parasitology
Since 2010 two global reviews of malaria research have recognized that local elimination and eradication of Plasmodium parasites are key drivers for further experimentation. To achieve these ambitious objectives it is universally recognized we must reduce malaria transmission through the mosquito vectors. A plethora of new laboratory assays are being developed to interrogate malaria transmission from the gametocyte to the sporozoite stage: assays that augment well-established field protocols to determine the entomological inoculation rate. However, the diverse readouts of these assays are not directly comparable. Here we attempt to identify the utility of each assay and provide rational frameworks by which to compare the impacts recorded by the diverse methodologies.
Churcher TS, Blagborough AM, Delves M, et al., 2012, Measuring the blockade of malaria transmission - an analysis of the standard membrane feeding assay, Int J Parasitol, Vol: 42, Pages: 1037-1044
The Standard Membrane Feeding Assay (SMFA) is currently considered to be the 'gold standard' for assessing the effectiveness of malaria transmission blocking interventions (TBIs) in vivo. The operation and analysis of SMFAs has varied between laboratories: field scientists often measure TBI efficacy as a reduction in the prevalence of infected mosquitoes whilst laboratory scientists are more likely to quote efficacy as a change in the number of oocysts within the mosquito. These metrics give outputs that differ widely, resulting in a need for greater understanding of how the SMFA informs TBI assessment. Using data from 536 different assays (conducted on Plasmodium falciparum and Plasmodiumberghei, in either Anopheles gambiae or Anopheles stephensi) it is shown that the relationship between these metrics is complex, yet predictable. Results demonstrate that the distribution of oocysts between mosquitoes is highly aggregated, making efficacy estimates based on reductions in intensity highly uncertain. Analysis of 30 SMFAs carried out on the same TBI confirms that the observed reduction in prevalence depends upon the parasite exposure (as measured by oocyst intensity in the control group), with assays which have lower exposure appearing more effective. By contrast, if efficacy is estimated as a reduction in oocyst intensity, then this candidate demonstrated constant efficacy, irrespective of the exposure level. To report transmission-blockade efficacy accurately, the results of SMFAs should give both the prevalence and intensity of oocysts in both the control and intervention group. Candidates should be assessed against a range of parasite exposures to allow laboratory results to be extrapolated to different field situations. Currently, many studies assessing TBIs are underpowered and uncertainties in efficacy estimates rarely reported. Statistical techniques that account for oocyst over-dispersion can reduce the number of mosquitoes that need to be dissected and allow
Delves MJ, Ramakrishnan C, Blagborough AM, et al., 2012, A high-throughput assay for the identification of malarial transmission-blocking drugs and vaccines, Int J Parasitol
Following the cessation of the global malaria eradication initiative in the 1970s, the prime objective of malarial intervention has been to reduce morbidity and mortality. This motivated the development of high throughput assays to determine the impact of interventions on asexual bloodstage parasites. In response to the new eradication agenda, interrupting parasite transmission from the human to the mosquito has been recognised as an important and additional target for intervention. Current assays for Plasmodium mosquito stage development are very low throughput and resource intensive, and are therefore inappropriate for high throughput screening. Using an ookinete-specific GFP reporter strain of the rodent parasite Plasmodium berghei, it has been possible to develop and validate a high biological complexity, high throughput bioassay that can rapidly, reproducibly and accurately evaluate the effect of transmission-blocking drugs or vaccines on the ability of host-derived gametocytes to undergo the essential onward steps of gamete formation, fertilization and ookinete maturation. This assay may greatly accelerate the development of malaria transmission-blocking interventions.
Goodman AL, Blagborough AM, Biswas S, et al., 2011, A viral vectored prime-boost immunization regime targeting the malaria pfs25 antigen induces transmission-blocking activity, PLOS One, Vol: 6, ISSN: 1932-6203
The ookinete surface protein Pfs25 is a macrogamete-to-ookinete/ookinete stage antigen of Plasmodium falciparum,capable of exerting high-level anti-malarial transmission-blocking activity following immunization with recombinantprotein-in-adjuvant formulations. Here, this antigen was expressed in recombinant chimpanzee adenovirus 63 (ChAd63),human adenovirus serotype 5 (AdHu5) and modified vaccinia virus Ankara (MVA) viral vectored vaccines. Twoimmunizations were administered to mice in a heterologous prime-boost regime. Immunization of mice with AdHu5Pfs25 at week 0 and MVA Pfs25 at week 10 (Ad-MVA Pfs25) resulted in high anti-Pfs25 IgG titers, consisting of predominantlyisotypes IgG1 and IgG2a. A single priming immunization with ChAd63 Pfs25 was as effective as AdHu5 Pfs25 with respect toELISA titers at 8 weeks post-immunization. Sera from Ad-MVA Pfs25 immunized mice inhibited the transmission of P.falciparum to the mosquito both ex vivo and in vivo. In a standard membrane-feeding assay using NF54 strain P. falciparum,oocyst intensity in Anopheles stephensi mosquitoes was significantly reduced in an IgG concentration-dependent mannerwhen compared to control feeds (96% reduction of intensity, 78% reduction in prevalence at a 1 in 5 dilution of sera). Inaddition, an in vivo transmission-blocking effect was also demonstrated by direct feeding of immunized mice infected withPfs25DR3, a chimeric P. berghei line expressing Pfs25 in place of endogenous Pbs25. In this assay the density of Pfs25DR3oocysts was significantly reduced when mosquitoes were fed on vaccinated as compared to control mice (67% reduction ofintensity, 28% reduction in prevalence) and specific IgG titer correlated with efficacy. These data confirm the utility of theadenovirus-MVA vaccine platform for the induction of antibodies with transmission-blocking activity, and support thecontinued development of this alternative approach to transmission-blocking malaria subunit vaccines.
Sheehy S, Duncan C, Anagnostou N, et al., 2011, CLINICAL EVALUATION OF NEW VIRAL VECTORED VACCINES TARGETING THE PLASMODIUM FALCIPARUM BLOOD-STAGE ANTIGENS; MSP1 AND AMA1, JOURNAL OF INFECTION, Vol: 63, Pages: 492-493, ISSN: 0163-4453
Talman AM, Lacroix C, Marques SR, et al., 2011, PbGEST mediates malaria transmission to both mosquito and vertebrate host, MOLECULAR MICROBIOLOGY, Vol: 82, Pages: 462-474, ISSN: 0950-382X
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- Citations: 69
Ramakrishnan C, Dessens JT, Armson R, et al., 2011, Vital functions of the malarial ookinete protein, CTRP, reside in the A domains, INTERNATIONAL JOURNAL FOR PARASITOLOGY, Vol: 41, Pages: 1029-1039, ISSN: 0020-7519
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- Citations: 24
Sheehy SH, Duncan CJ, Elias S, et al., 2010, HETEROLOGOUS PRIME-BOOST VACCINATION WITH ADCH63 AND MVA EXPRESSING MSP1 CAN INDUCE PROTECTIVE EFFICACY AGAINST SPOROZOITE CHALLENGE IN VOLUNTEERS, 59th Annual Meeting of the American-Society-of-Tropical-Medicine-and-Hygiene (ASTMH), Publisher: AMER SOC TROP MED & HYGIENE, Pages: 48-49, ISSN: 0002-9637
Kambris Z, Blagborough AM, Pinto SB, et al., 2010, Wolbachia stimulates immune gene expression and inhibits Plasmodium development in Anopheles gambiae, Plos Pathogens, Vol: 6, ISSN: 1553-7374
The over-replicating wMelPop strain of the endosymbiont Wolbachia pipientis has recently been shown to be capable ofinducing immune upregulation and inhibition of pathogen transmission in Aedes aegypti mosquitoes. In order to examinewhether comparable effects would be seen in the malaria vector Anopheles gambiae, transient somatic infections ofwMelPop were created by intrathoracic inoculation. Upregulation of six selected immune genes was observed compared tocontrols, at least two of which (LRIM1 and TEP1) influence the development of malaria parasites. A stably infected An.gambiae cell line also showed increased expression of malaria-related immune genes. Highly significant reductions inPlasmodium infection intensity were observed in the wMelPop-infected cohort, and using gene knockdown, evidence forthe role of TEP1 in this phenotype was obtained. Comparing the levels of upregulation in somatic and stably inheritedwMelPop infections in Ae. aegypti revealed that levels of upregulation were lower in the somatic infections than in the stablytransinfected line; inhibition of development of Brugia filarial nematodes was nevertheless observed in the somaticwMelPop infected females. Thus we consider that the effects observed in An. gambiae are also likely to be more pronouncedif stably inherited wMelPop transinfections can be created, and that somatic infections of Wolbachia provide a useful modelfor examining effects on pathogen development or dissemination. The data are discussed with respect to the comparativeeffects on malaria vectorial capacity of life shortening and direct inhibition of Plasmodium development that can beproduced by Wolbachia.
Blagborough AM, Yoshida S, Sattabongkot J, et al., 2010, Intranasal and intramuscular immunization with Baculovirus Dual Expression System-based Pvs25 vaccine substantially blocks <i>Plasmodium</i> <i>vivax</i> transmission, VACCINE, Vol: 28, Pages: 6014-6020, ISSN: 0264-410X
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- Citations: 42
Talman AM, Blagborough AM, Sinden RE, 2010, A Plasmodium falciparum strain expressing GFP throughout the parasite’s life-cycle, PLOS One, Vol: 5, ISSN: 1932-6203
The human malaria parasite Plasmodium falciparum is responsible for the majority of malaria-related deaths. Tools allowingthe study of the basic biology of P. falciparum throughout the life cycle are critical to the development of new strategies totarget the parasite within both human and mosquito hosts. We here present 3D7HT-GFP, a strain of P. falciparumconstitutively expressing the Green Fluorescent Protein (GFP) throughout the life cycle, which has retained its capacity tocomplete sporogonic development. The GFP expressing cassette was inserted in the Pf47 locus. Using this transgenic strain,parasite tracking and population dynamics studies in mosquito stages and exo-erythrocytic schizogony is greatly facilitated.The development of 3D7HT-GFP will permit a deeper understanding of the biology of parasite-host vector interactions, andfacilitate the development of high-throughput malaria transmission assays and thus aid development of new interventionstrategies against both parasite and mosquito.
Blagborough AM, Sinden RE, 2009, <i>Plasmodium berghei</i> HAP2 induces strong malaria transmission-blocking immunity <i>in vivo</i> and <i>in vitro</i>, VACCINE, Vol: 27, Pages: 5187-5194, ISSN: 0264-410X
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- Citations: 81
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