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malaria transmission blocking

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https://www.readbyqxmd.com/read/28646324/expression-purification-and-characterization-of-gmz2-10c-a-complex-disulphide-bonded-fusion-protein-vaccine-candidate-against-the-asexual-and-sexual-life-stages-of-the-malaria-causing-plasmodium-falciparum-parasite
#1
Ulrik H Mistarz, Susheel K Singh, Tam T T N Nguyen, Will Roeffen, Fen Yang, Casper Lissau, Søren M Madsen, Astrid Vrang, Régis W Tiendrebeogo, Ikhlaq H Kana, Robert W Sauerwein, Michael Theisen, Kasper D Rand
PURPOSE: Production and characterization of a chimeric fusion protein (GMZ2'.10C) which combines epitopes of key malaria parasite antigens: glutamate-rich protein (GLURP), merozoite surface protein 3 (MSP3), and the highly disulphide bonded Pfs48/45 (10C). GMZ2'.10C is a potential candidate for a multi-stage malaria vaccine that targets both transmission and asexual life-cycle stages of the parasite. METHODS: GMZ2'.10C was produced in Lactococcus lactis and purified using either an immunoaffinity purification (IP) or a conventional purification (CP) method...
June 23, 2017: Pharmaceutical Research
https://www.readbyqxmd.com/read/28630474/nanoassembly-routes-stimulate-conflicting-antibody-quantity-and-quality-for-transmission-blocking-malaria-vaccines
#2
Darren B Leneghan, Kazutoyo Miura, Iona J Taylor, Yuanyuan Li, Jing Jin, Karl D Brune, Martin F Bachmann, Mark Howarth, Carole A Long, Sumi Biswas
Vaccine development efforts have recently focused on enabling strong immune responses to poorly immunogenic antigens, via display on multimerisation scaffolds or virus like particles (VLPs). Typically such studies demonstrate improved antibody titer comparing monomeric and nano-arrayed antigen. There are many such studies and scaffold technologies, but minimal side-by-side evaluation of platforms for both the amount and efficacy of antibodies induced. Here we present direct comparison of three leading platforms displaying the promising malaria transmission-blocking vaccine (TBV) target Pfs25...
June 19, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28619071/new-adenovirus-based-vaccine-vectors-targeting-pfs25-elicit-antibodies-that-inhibit-plasmodium-falciparum-transmission
#3
Kathleen A McGuire, Kazutoyo Miura, Christopher M Wiethoff, Kim C Williamson
BACKGROUND: An effective malaria transmission-blocking vaccine (TBV) would be a major advance in the current efforts to eliminate and, ultimately, eradicate malaria. Antibodies against Plasmodium falciparum surface protein, Pfs25, are known to block parasite development in the mosquito vector. However, in initial clinical trials the limited immunogenicity of recombinant Pfs25 protein-in-adjuvant vaccines has been a challenge. METHODS: Novel human adenovirus type 5 (Ad5) vectors were used in heterologous prime boost vaccination strategies to augment the immune response against Pfs25...
June 15, 2017: Malaria Journal
https://www.readbyqxmd.com/read/28617253/the-emerging-role-of-the-human-bone-marrow-as-a-privileged-developmental-niche-for-the-transmission-stages-of-the-malaria-parasite-plasmodium-falciparum-commentary
#4
Pietro Alano
The spread of malaria relies on the ability of the Plasmodium parasites to be transmitted from infected individuals to the Anopheles mosquito vectors. Recent work on the most lethal of the malaria parasites, Plasmodium falciparum, identified the infected human bone marrow as a preferential site for the localization and maturation of the parasite transmission stages, the gametocytes. These findings unveil a complex host parasite interplay and an unsuspected role of the bone marrow microenvironment in the successful transmission of the malaria parasite and have major implications in developing and targeting future interventions to block the transmission of P...
April 2017: Annali Dell'Istituto Superiore di Sanità
https://www.readbyqxmd.com/read/28607435/preferential-suppression-of-anopheles-gambiae-host-sequences-allows-detection-of-the-mosquito-eukaryotic-microbiome
#5
Eugeni Belda, Boubacar Coulibaly, Abdrahamane Fofana, Abdoul H Beavogui, Sekou F Traore, Daryl M Gohl, Kenneth D Vernick, Michelle M Riehle
Anopheles mosquitoes are vectors of the human malaria parasite, Plasmodium falciparum. The vector microbiota is a likely factor influencing parasite transmission. The prokaryotic microbiota of mosquitoes is efficiently surveyed by sequencing of hypervariable regions of the 16s ribosomal RNA (rRNA) gene. However, identification of the eukaryotic microbiota by targeting the 18s rRNA gene is challenging due to simultaneous amplification of the abundant 18s rRNA gene target in the mosquito host. Consequently, the eukaryotic microbial diversity of mosquitoes is vastly underexplored...
June 12, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28591198/single-dose-primaquine-to-reduce-gametocyte-carriage-and-plasmodium-falciparum-transmission-in-cambodia-an-open-label-randomized-trial
#6
Jessica T Lin, Chanthap Lon, Michele D Spring, Somethy Sok, Soklyda Chann, Mali Ittiverakul, Worachet Kuntawunginn, Mok My, Kheangheng Thay, Rifat Rahman, Sujata Balasubramanian, Mengchuor Char, Charlotte A Lanteri, Panita Gosi, Ratawan Ubalee, Steven R Meshnick, David L Saunders
BACKGROUND: Single low dose primaquine (SLD PQ, 0.25mg/kg) is recommended in combination with artemisinin-based combination therapy (ACT) as a gametocytocide to prevent Plasmodium falciparum transmission in areas threatened by artemisinin resistance. To date, no randomized controlled trials have measured primaquine's effect on infectiousness to Anopheline mosquitoes in Southeast Asia. METHODS: Cambodian adults with uncomplicated falciparum malaria were randomized to receive a single 45mg dose of primaquine (equivalent to three SLD PQ) or no primaquine after the third dose of dihydroartemisin-piperaquine (DHP) therapy...
2017: PloS One
https://www.readbyqxmd.com/read/28583072/identification-of-candidate-transmission-blocking-antigen-genes-in-theileria-annulata-and-related-vector-borne-apicomplexan-parasites
#7
Laetitia Lempereur, Stephen D Larcombe, Zeeshan Durrani, Tulin Karagenc, Huseyin Bilgin Bilgic, Serkan Bakirci, Selin Hacilarlioglu, Jane Kinnaird, Joanne Thompson, William Weir, Brian Shiels
BACKGROUND: Vector-borne apicomplexan parasites are a major cause of mortality and morbidity to humans and livestock globally. The most important disease syndromes caused by these parasites are malaria, babesiosis and theileriosis. Strategies for control often target parasite stages in the mammalian host that cause disease, but this can result in reservoir infections that promote pathogen transmission and generate economic loss. Optimal control strategies should protect against clinical disease, block transmission and be applicable across related genera of parasites...
June 5, 2017: BMC Genomics
https://www.readbyqxmd.com/read/28578824/improving-the-malaria-transmission-blocking-activity-of-a-plasmodium-falciparum-48-45-based-vaccine-antigen-by-spytag-spycatcher-mediated-virus-like-display
#8
Susheel K Singh, Susan Thrane, Christoph M Janitzek, Morten A Nielsen, Thor G Theander, Michael Theisen, Ali Salanti, Adam F Sander
Malaria is a devastating disease caused by Plasmodium parasites, resulting in almost 0.5 million deaths per year. The Pfs48/45 protein exposed on the P. falciparum sexual stages is one of the most advanced antigen candidates for a transmission-blocking (TB) vaccine in the clinical pipeline. However, it remains essential to identify an optimal vaccine formulation that can facilitate induction of a long-lasting TB anti-Pfs48/45 response. Here we report on the development and evaluation of two Pfs48/45-based virus-like particle (VLP) vaccines generated using the AP205 SpyTag/Catcher VLP system...
May 31, 2017: Vaccine
https://www.readbyqxmd.com/read/28573466/wolbachia-spreading-dynamics-in-mosquitoes-with-imperfect-maternal-transmission
#9
Bo Zheng, Moxun Tang, Jianshe Yu, Junxiong Qiu
Mosquitoes are primary vectors of life-threatening diseases such as dengue, malaria, and Zika. A new control method involves releasing mosquitoes carrying bacterium Wolbachia into the natural areas to infect wild mosquitoes and block disease transmission. In this work, we use differential equations to describe Wolbachia spreading dynamics, focusing on the poorly understood effect of imperfect maternal transmission. We establish two useful identities and employ them to prove that the system exhibits monomorphic, bistable, and polymorphic dynamics, and give sufficient and necessary conditions for each case...
June 1, 2017: Journal of Mathematical Biology
https://www.readbyqxmd.com/read/28569168/construct-design-production-and-characterization-of-plasmodium-falciparum-48-45-r0-6c-subunit-protein-produced-in-lactococcus-lactis-as-candidate-vaccine
#10
Susheel K Singh, Will Roeffen, Ulrik H Mistarz, Bishwanath Kumar Chourasia, Fen Yang, Kasper D Rand, Robert W Sauerwein, Michael Theisen
BACKGROUND: The sexual stages of Plasmodium falciparum are responsible for the spread of the parasite in malaria endemic areas. The cysteine-rich Pfs48/45 protein, exposed on the surface of sexual stages, is one of the most advanced antigens for inclusion into a vaccine that will block transmission. However, clinical Pfs48/45 sub-unit vaccine development has been hampered by the inability to produce high yields of recombinant protein as the native structure is required for the induction of functional transmission-blocking (TB) antibodies...
May 31, 2017: Microbial Cell Factories
https://www.readbyqxmd.com/read/28560696/impact-of-the-charge-ratio-on-the-in-vivo-immunogenicity-of-lipoplexes
#11
Zahra Heidari, Jaspreet S Arora, Dibyadyuti Datta, Vijay T John, Nirbhay Kumar, Geetha P Bansal
PURPOSE: The present study investigated the immunogenic potential of different cationic liposome formulations with a DNA plasmid encoding Pfs25, a malaria transmission-blocking vaccine candidate. METHODS: Pfs25 plasmid DNA was complexed with cationic liposomes to produce lipoplexes at different charge ratios of the cationic lipid head group to the nucleotide phosphate (N:P). The formation of lipoplexes was visualized by Cryogenic-TEM. Confocal microscopy of lipoplexes formed with GFP encoding plasmid DNA, and flow cytometry was used to determine their in vitro transfection capability...
May 30, 2017: Pharmaceutical Research
https://www.readbyqxmd.com/read/28559405/plasmodium-berghei-pimms2-promotes-ookinete-invasion-of-the-anopheles-gambiae-mosquito-midgut
#12
Chiamaka V Ukegbu, Karolina A Akinosoglou, George K Christophides, Dina Vlachou
Mosquito midgut stages of the malaria parasite present an attractive biological system to study host-parasite interactions and develop interventions to block disease transmission. Mosquito infection ensues upon oocyst development that follows ookinete invasion and traversal of the mosquito midgut epithelium. Here, we report the characterization of PIMMS2 (Plasmodium Invasion of Mosquito Midgut Screen candidate 2), a Plasmodium berghei protein with structural similarities to subtilisin-like proteins. PIMMS2 orthologs are present in the genomes of all plasmodia and are mapped between the subtilisin-encoding genes SUB1 and SUB3P...
May 30, 2017: Infection and Immunity
https://www.readbyqxmd.com/read/28533429/fibrinogen-domain-of-frep1-is-a-broad-spectrum-malaria-transmission-blocking-vaccine-antigen
#13
Guodong Niu, Caio Franca, Genwei Zhang, Wanlapa Roobsoong, Wang Nguitragool, Xiaohong Wang, Jetsumon Prachumsri, Noah S Butler, Jun Li
FREP1 in mosquito midguts facilitates P. falciparum parasite transmission. Fibrinogen-like (FBG) domain of FREP1 is highly conserved (>90% identical) among Anopheles species from different continents, suggesting that anti-FBG antibodies may block malaria transmission to all anopheline mosquitoes. Using standard membrane-feeding assays, anti-FREP1 polyclonal antibodies significantly blocked transmission of P. berghei and P. vivax to An. gambiae and An. dirus respectively. Furthermore, in vivo studies of mice immunized with FBG achieved >75% blocking efficacy of P...
May 22, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28526047/the-paradigm-of-eave-tubes-scaling-up-house-improvement-and-optimizing-insecticide-delivery-against-disease-transmitting-mosquitoes
#14
Fredros Okumu
Control of mosquito-borne diseases is greatly compromised by spread of insecticide resistance, high implementation costs and sub-optimal compliance among users. Improved housing has potential to reduce malaria transmission nearly as much as long-lasting insecticide-treated nets (LLINs), while also preventing other arthropod-borne diseases and improving overall well-being. Yet, it is hardly promoted as mainstream intervention, partly because of high costs, minimal communal benefits to people in non-improved houses, and low scalability...
May 19, 2017: Malaria Journal
https://www.readbyqxmd.com/read/28513586/hundreds-of-dual-stage-antimalarial-molecules-discovered-by-a-functional-gametocyte-screen
#15
Celia Miguel-Blanco, Irene Molina, Ana I Bardera, Beatriz Díaz, Laura de Las Heras, Sonia Lozano, Carolina González, Janneth Rodrigues, Michael J Delves, Andrea Ruecker, Gonzalo Colmenarejo, Sara Viera, María S Martínez-Martínez, Esther Fernández, Jake Baum, Robert E Sinden, Esperanza Herreros
Plasmodium falciparum stage V gametocytes are responsible for parasite transmission, and drugs targeting this stage are needed to support malaria elimination. We here screen the Tres Cantos Antimalarial Set (TCAMS) using the previously developed P. falciparum female gametocyte activation assay (Pf FGAA), which assesses stage V female gametocyte viability and functionality using Pfs25 expression. We identify over 400 compounds with activities <2 μM, chemically classified into 57 clusters and 33 singletons...
May 17, 2017: Nature Communications
https://www.readbyqxmd.com/read/28479180/accelerated-and-long-term-stability-study-of-pfs25-epa-conjugates-adjuvanted-with-alhydrogel%C3%A2
#16
Daming Zhu, Yimin Wu, Holly McClellan, Weili Dai, Kelly Rausch, Dominique Jones, Joan Aebig, Emma Barnafo, Brandi Butler, Lynn Lambert, David L Narum, Patrick E Duffy
Pfs25, a Plasmodium falciparum surface protein expressed during zygote and ookinete stages in infected mosquitoes, is a lead transmission-blocking vaccine candidate against falciparum malaria. To enhance immunogenicity, recombinant Pfs25 was chemically conjugated to recombinant nontoxic Pseudomonas aeruginosa ExoProtein A (rEPA) in conformance with current good manufacturing practices (cGMP), and formulated with the alum adjuvant Alhydrogel. In order to meet the regulatory requirements for a phase 1 human clinical trial, the vaccine product was extensively evaluated for stability at an initial time point and through the clinical trial period annually...
May 31, 2017: Vaccine
https://www.readbyqxmd.com/read/28464929/the-development-of-sexual-stage-malaria-gametocytes-in-a-wave-bioreactor
#17
Corine G Demanga, Jenny W L Eng, Donald L Gardiner, Alison Roth, Alice Butterworth, John H Adams, Katharine R Trenholme, John P Dalton
BACKGROUND: Blocking malaria gametocyte development in RBCs or their fertilization in the mosquito gut can prevent infection of the mosquito vector and passage of disease to the human host. A 'transmission blocking' strategy is a component of future malaria control. However, the lack of robust culture systems for producing large amounts of Plasmodium falciparum gametocytes has limited our understanding of sexual-stage malaria biology and made vaccine or chemotherapeutic discoveries more difficult...
May 2, 2017: Parasites & Vectors
https://www.readbyqxmd.com/read/28455236/genomics-and-epigenetics-of-sexual-commitment-in-plasmodium
#18
REVIEW
D P Bechtsi, A P Waters
Malaria is the disease caused by the apicomplexan parasites belonging to the genus Plasmodium. Expanding our arsenal to include transmission-blocking agents in our fight against malaria is becoming increasingly important. Such an implementation requires detailed understanding of the biology of the Plasmodium life cycle stages that are transmissible. Plasmodium gametocytes are the only parasite stage that can be transmitted to the mosquito vector and are the product of sexual development in a small percentage of parasites that continually proliferate in host blood...
April 26, 2017: International Journal for Parasitology
https://www.readbyqxmd.com/read/28446690/antimalarial-efficacy-of-mmv390048-an-inhibitor-of-plasmodium-phosphatidylinositol-4-kinase
#19
Tanya Paquet, Claire Le Manach, Diego González Cabrera, Yassir Younis, Philipp P Henrich, Tara S Abraham, Marcus C S Lee, Rajshekhar Basak, Sonja Ghidelli-Disse, María José Lafuente-Monasterio, Marcus Bantscheff, Andrea Ruecker, Andrew M Blagborough, Sara E Zakutansky, Anne-Marie Zeeman, Karen L White, David M Shackleford, Janne Mannila, Julia Morizzi, Christian Scheurer, Iñigo Angulo-Barturen, María Santos Martínez, Santiago Ferrer, Laura María Sanz, Francisco Javier Gamo, Janette Reader, Mariette Botha, Koen J Dechering, Robert W Sauerwein, Anchalee Tungtaeng, Pattaraporn Vanachayangkul, Chek Shik Lim, Jeremy Burrows, Michael J Witty, Kennan C Marsh, Christophe Bodenreider, Rosemary Rochford, Suresh M Solapure, María Belén Jiménez-Díaz, Sergio Wittlin, Susan A Charman, Cristina Donini, Brice Campo, Lyn-Marie Birkholtz, Kirsten K Hanson, Gerard Drewes, Clemens H M Kocken, Michael J Delves, Didier Leroy, David A Fidock, David Waterson, Leslie J Street, Kelly Chibale
As part of the global effort toward malaria eradication, phenotypic whole-cell screening revealed the 2-aminopyridine class of small molecules as a good starting point to develop new antimalarial drugs. Stemming from this series, we found that the derivative, MMV390048, lacked cross-resistance with current drugs used to treat malaria. This compound was efficacious against all Plasmodium life cycle stages, apart from late hypnozoites in the liver. Efficacy was shown in the humanized Plasmodium falciparum mouse model, and modest reductions in mouse-to-mouse transmission were achieved in the Plasmodium berghei mouse model...
April 26, 2017: Science Translational Medicine
https://www.readbyqxmd.com/read/28437083/dual-plug-and-display-synthetic-assembly-using-orthogonal-reactive-proteins-for-twin-antigen-immunization
#20
Karl D Brune, Can M Buldun, Yuanyuan Li, Iona J Taylor, Florian Brod, Sumi Biswas, Mark Howarth
Engineering modular platforms to control biomolecular architecture can advance both the understanding and the manipulation of biological systems. Icosahedral particles uniformly displaying single antigens stimulate potent immune activation and have been successful in various licensed vaccines. However, it remains challenging to display multiple antigens on a single particle and to induce broader immunity protective across strains or even against distinct diseases. Here, we design a dually addressable synthetic nanoparticle by engineering the multimerizing coiled-coil IMX313 and two orthogonally reactive split proteins...
May 5, 2017: Bioconjugate Chemistry
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