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https://www.readbyqxmd.com/read/28791254/transcriptional-profiling-defines-histone-acetylation-as-a-regulator-of-gene-expression-during-human-to-mosquito-transmission-of-the-malaria-parasite-plasmodium-falciparum
#1
Che J Ngwa, Meike J Kiesow, Olga Papst, Lindsey M Orchard, Michael Filarsky, Alina N Rosinski, Till S Voss, Manuel Llinás, Gabriele Pradel
Transmission of the malaria parasite Plasmodium falciparum from the human to the mosquito is mediated by the intraerythrocytic gametocytes, which, once taken up during a blood meal, become activated to initiate sexual reproduction. Because gametocytes are the only parasite stages able to establish an infection in the mosquito, they are crucial for spreading the tropical disease. During gametocyte maturation, different repertoires of genes are switched on and off in a well-coordinated sequence, pointing to regulatory mechanisms of gene expression...
2017: Frontiers in Cellular and Infection Microbiology
https://www.readbyqxmd.com/read/28754921/evaluation-of-two-lead-malaria-transmission-blocking-vaccine-candidate-antibodies-in-natural-parasite-vector-combinations
#2
Anais Bompard, Dari F Da, Rakiswendé S Yerbanga, Sumi Biswas, Melissa Kapulu, Teun Bousema, Thierry Lefèvre, Anna Cohuet, Thomas S Churcher
Transmission blocking vaccines (TBV) which aim to control malaria by inhibiting human-to-mosquito transmission show considerable promise though their utility against naturally circulating parasites remains unknown. The efficacy of two lead candidates targeting Pfs25 and Pfs230 antigens to prevent onwards transmission of naturally occurring parasites to a local mosquito strain is assessed using direct membrane feeding assays and murine antibodies in Burkina Faso. The transmission blocking activity of both candidates depends on the level of parasite exposure (as assessed by the mean number of oocysts in control mosquitoes) and antibody titers...
July 28, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28722588/optimizing-direct-membrane-and-direct-skin-feeding-assays-for-plasmodium-falciparum-transmission-blocking-vaccine-trials-in-bancoumana-mali
#3
Mamadou B Coulibaly, Erin E Gabriel, Youssouf Sinaba, Daman Sylla, Adama Sacko, Lakamy Sylla, Boubacar Coulibaly, Jen C C Hume, Ibrahima Baber, Mahamadoun H Assadou, Issaka Sagara, Yimin Wu, Sara A Healy, Ogobara Doumbo, Sekou F Traore, Patrick E Duffy
Malaria transmission-blocking vaccines (TBV) have been evaluated in field trials in Mali, since 2013. However, the assays currently used to measure serum antibody TB activity (TBA) after vaccination are highly variable, in part due to the lack of optimization and standardization for field assays in which mosquitoes feed on gametocytemic blood. Herein, we report a study conducted in Bancoumana village, Mali, where we identify and optimize the parameters that contribute to successful mosquito feeding outcomes in both direct skin feeds (DSFs) and direct membrane feeding assays (DMFA)...
June 26, 2017: American Journal of Tropical Medicine and Hygiene
https://www.readbyqxmd.com/read/28630474/nanoassembly-routes-stimulate-conflicting-antibody-quantity-and-quality-for-transmission-blocking-malaria-vaccines
#4
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
#5
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/28578824/improving-the-malaria-transmission-blocking-activity-of-a-plasmodium-falciparum-48-45-based-vaccine-antigen-by-spytag-spycatcher-mediated-virus-like-display
#6
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/28560696/impact-of-the-charge-ratio-on-the-in-vivo-immunogenicity-of-lipoplexes
#7
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...
September 2017: Pharmaceutical Research
https://www.readbyqxmd.com/read/28533429/the-fibrinogen-like-domain-of-frep1-protein-is-a-broad-spectrum-malaria-transmission-blocking-vaccine-antigen
#8
Guodong Niu, Caio Franc A, Genwei Zhang, Wanlapa Roobsoong, Wang Nguitragool, Xiaohong Wang, Jetsumon Prachumsri, Noah S Butler, Jun Li
FREP1 in mosquito midguts facilitates Plasmodium falciparum parasite transmission. The 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 Plasmodium berghei and Plasmodium vivax to Anopheles gambiae and Anopheles dirus, respectively...
July 14, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28378767/the-need-to-compare-assessing-the-level-of-agreement-of-three-high-throughput-assays-against-plasmodium-falciparum-mature-gametocytes
#9
Leonardo Lucantoni, Sasdekumar Loganathan, Vicky M Avery
Whole-cell High-Throughput Screening (HTS) is a key tool for the discovery of much needed malaria transmission blocking drugs. Discrepancies in the reported outcomes from various HTS Plasmodium falciparum gametocytocidal assays hinder the direct comparison of data and ultimately the interpretation of the transmission blocking potential of hits. To dissect the underlying determinants of such discrepancies and assess the impact that assay-specific factors have on transmission-blocking predictivity, a 39-compound subset from the Medicines for Malaria Venture Malaria Box was tested in parallel against three distinct mature stage gametocytocidal assays, under strictly controlled parasitological, chemical, temporal and analytical conditions resembling the standard membrane feeding assay (SMFA)...
April 5, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28209188/erratum-to-characterization-of-a-plasmodium-berghei-sexual-stage-antigen-pbph-as-a-new-candidate-for-malaria-transmission-blocking-vaccine
#10
Xu Kou, Wenqi Zheng, Feng Du, Fei Liu, Meilian Wang, Qi Fan, Liwang Cui, Enjie Luo, Yaming Cao
No abstract text is available yet for this article.
February 16, 2017: Parasites & Vectors
https://www.readbyqxmd.com/read/28057055/functional-characterization-of-plasmodium-berghei-psop25-during-ookinete-development-and-as-a-malaria-transmission-blocking-vaccine-candidate
#11
Wenqi Zheng, Fei Liu, Yiwen He, Qingyang Liu, Gregory B Humphreys, Takafumi Tsuboi, Qi Fan, Enjie Luo, Yaming Cao, Liwang Cui
BACKGROUND: Plasmodium ookinete surface proteins as post-fertilization target antigens are potential malaria transmission-blocking vaccine (TBV) candidates. Putative secreted ookinete protein 25 (PSOP25) is a highly conserved ookinete surface protein, and has been shown to be a promising novel TBV target. Here, we further investigated the TBV activities of the full-length recombinant PSOP25 (rPSOP25) protein in Plasmodium berghei, and characterized the potential functions of PSOP25 during the P...
January 5, 2017: Parasites & Vectors
https://www.readbyqxmd.com/read/27978709/a-malaria-transmission-blocking-usnic-acid-derivative-prevents-plasmodium-zygote-to-ookinete-maturation-in-the-mosquito-midgut
#12
Rebecca Pastrana-Mena, Derrick K Mathias, Michael Delves, Krithika Rajaram, Jonas G King, Rebecca Yee, Beatrice Trucchi, Luisella Verotta, Rhoel R Dinglasan
The evolution of drug resistance is a recurrent problem that has plagued efforts to treat and control malaria. Recent emergence of artemisinin resistance in Southeast Asia underscores the need to develop novel antimalarials and identify new targetable pathways in Plasmodium parasites. Transmission-blocking approaches, which typically target gametocytes in the host bloodstream or parasite stages in the mosquito gut, are recognized collectively as a strategy that when used in combination with antimalarials that target erythrocytic stages will not only cure malaria but will also prevent subsequent transmission...
December 16, 2016: ACS Chemical Biology
https://www.readbyqxmd.com/read/27903741/whole-killed-blood-stage-vaccine-induced-immunity-suppresses-the-development-of-malaria-parasites-in-mosquitoes
#13
Feng Zhu, Taiping Liu, Chenhao Zhao, Xiao Lu, Jian Zhang, Wenyue Xu
As a malaria transmission-blocking vaccine alone does not confer a direct benefit to the recipient, it is necessary to develop a vaccine that not only blocks malaria transmission but also protects vaccinated individuals. In this study we observed that a whole-killed blood-stage vaccine (WKV) not only conferred protection against the blood-stage challenge but also markedly inhibited the transmission of different strains of the malaria parasite. Although the parasitemia is much lower in WKV-immunized mice challenged with malaria parasites, the gametocytemia is comparable between control and immunized mice during the early stages of infection...
January 1, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/27780638/5-aminopyrazole-4-carboxamide-analogues-are-selective-inhibitors-of-plasmodium-falciparum-microgametocyte-exflagellation-and-potential-malaria-transmission-blocking-agents
#14
Wenlin Huang, Matthew A Hulverson, Zhongsheng Zhang, Ryan Choi, Kevin J Hart, Mark Kennedy, Rama Subba Rao Vidadala, Dustin J Maly, Wesley C Van Voorhis, Scott E Lindner, Erkang Fan, Kayode K Ojo
Plasmodium falciparum calcium-dependent protein kinase 4 (PfCDPK4) is essential for the exflagellation of male gametocytes. Inhibition of PfCDPK4 is an effective way of blocking the transmission of malaria by mosquitoes. A series of 5-aminopyrazole-4-carboxamide analogues are demonstrated to be potent inhibitors of PfCDPK4. The compounds are also able to block exflagellation of Plasmodium falciparum male gametocytes without observable toxicity to mammalian cells.
November 15, 2016: Bioorganic & Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/27612458/an-inter-laboratory-comparison-of-standard-membrane-feeding-assays-for-evaluation-of-malaria-transmission-blocking-vaccines
#15
Kazutoyo Miura, Will J R Stone, Karin M Koolen, Bingbing Deng, Luwen Zhou, Geert-Jan van Gemert, Emily Locke, Merribeth Morin, Teun Bousema, Robert W Sauerwein, Carole A Long, Koen J Dechering
BACKGROUND: An effective malaria transmission-blocking vaccine may play an important role in malaria elimination efforts, and a robust biological assay is essential for its development. The standard membrane-feeding assay (SMFA) for Plasmodium falciparum infection of mosquitoes is considered a "gold standard" assay to measure transmission-blocking activity of test antibodies, and has been utilized widely in both non-clinical and clinical studies. While several studies have discussed the inherent variability of SMFA within a study group, there has been no assessment of inter-laboratory variation...
September 9, 2016: Malaria Journal
https://www.readbyqxmd.com/read/27491342/prevalence-of-plasmodium-falciparum-transmission-reducing-immunity-among-primary-school-children-in-a-malaria-moderate-transmission-region-in-zimbabwe
#16
Noah H Paul, Arthur Vengesai, Takafira Mduluza, James Chipeta, Nicholas Midzi, Geetha P Bansal, Nirbhay Kumar
Malaria continues to cause alarming morbidity and mortality in more than 100 countries worldwide. Antigens in the various life cycle stages of malaria parasites are presented to the immune system during natural infection and it is widely recognized that after repeated malaria exposure, adults develop partially protective immunity. Specific antigens of natural immunity represent among the most important targets for the development of malaria vaccines. Immunity against the transmission stages of the malaria parasite represents an important approach to reduce malaria transmission and is believed to become an important tool for gradual elimination of malaria...
November 2016: Acta Tropica
https://www.readbyqxmd.com/read/27458212/single-dose-primaquine-in-a-preclinical-model-of-glucose-6-phosphate-dehydrogenase-deficiency-implications-for-use-in-malaria-transmission-blocking-programs
#17
Kristina S Wickham, Paul C Baresel, Sean R Marcsisin, Jason Sousa, Chau T Vuong, Gregory A Reichard, Brice Campo, Babu L Tekwani, Larry A Walker, Rosemary Rochford
Individuals with glucose-6-phosphate dehydrogenase (G6PD) deficiency (G6PDd) are at risk for developing hemolytic anemia when given the antimalarial drug primaquine (PQ). The WHO Evidence Review Group released a report suggesting that mass administration of a single dose of PQ at 0.25 mg of base/kg of body weight (mpk) (mouse equivalent of 3.125 mpk) could potentially reduce malaria transmission based on its gametocytocidal activity and could be safely administered to G6PD-deficient individuals, but there are limited safety data available confirming the optimum single dose of PQ...
October 2016: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/27372156/transmission-blocking-activity-is-determined-by-transmission-reducing-activity-and-number-of-control-oocysts-in-plasmodium-falciparum-standard-membrane-feeding-assay
#18
Kazutoyo Miura, Bruce J Swihart, Bingbing Deng, Luwen Zhou, Thao P Pham, Ababacar Diouf, Timothy Burton, Michael P Fay, Carole A Long
Malaria transmission-blocking vaccines (TBVs) are potentially helpful tools for malaria eradication. The standard membrane-feeding assay (SMFA) is considered one of the "gold standard" assays for TBV development. However, lack of consensus in reporting results from SMFA has made it very challenging to compare results from different studies. Two main readouts, % inhibition in mean oocyst count per mosquito (TRA) and % inhibition in prevalence of infected mosquitoes (TBA), have been used widely. In this study, we statistically modeled the oocyst data in SMFA using data from 105 independent feeding experiments including 9804 mosquitoes...
July 29, 2016: Vaccine
https://www.readbyqxmd.com/read/27312996/translational-repression-of-the-cpw-wpc-gene-family-in-the-malaria-parasite-plasmodium
#19
Pavitra N Rao, Jorge M Santos, Arnab Pain, Thomas J Templeton, Gunnar R Mair
The technical challenges of working with the sexual stages of the malaria parasite Plasmodium have hindered the characterization of sexual stage antigens in the quest for a successful malaria transmission-blocking vaccine. One such predicted and largely uncharacterized group of sexual stage candidate antigens is the CPW-WPC family of proteins. CPW-WPC proteins are named for a characteristic domain that contains two conserved motifs, CPxxW and WPC. Conserved across Apicomplexa, this family is also present earlier in the Alveolata in the free-living, non-parasitophorous, photosynthetic chromerids, Chromera and Vitrella...
October 2016: Parasitology International
https://www.readbyqxmd.com/read/27239480/comparison-of-intranasal-outer-membrane-vesicles-with-cholera-toxin-and-injected-mf59c-1-as-adjuvants-for-malaria-transmission-blocking-antigens-anapn1-and-pfs48-45
#20
Michael Pritsch, Najib Ben-Khaled, Michael Chaloupka, Sebastian Kobold, Nicole Berens-Riha, Annabell Peter, Gabriele Liegl, Sören Schubert, Michael Hoelscher, Thomas Löscher, Andreas Wieser
Purified protein vaccines often require adjuvants for efficient stimulation of immune responses. There is no licensed mucosal adjuvant on the market to adequately boost the immune response to purified antigens for intranasal applications in humans. Bacterial outer membrane vesicles (OMV) are attractive candidates potentially combining antigenic and adjuvant properties in one substance. To more precisely characterize the potential of Escherichia coli OMV for intranasal vaccination with heterologous antigens, immune responses for AnAPN1 and Pfs48/45 as well as ovalbumin as a reference antigen were assessed in mice...
2016: Journal of Immunology Research
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