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"malaria transmission blocking"

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...
2016: Malaria Journal
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
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
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
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
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
Christian P Nixon
Malaria remains one of the most significant infectious diseases worldwide. Concordant with scaled intervention efforts and the emphasis of elimination and eradication on the agenda of many malaria control programs, the development of a malaria vaccine that reduces transmission of the parasite from human host to mosquito vector has been incorporated as an important new strategic goal. Transmission of malaria from man to mosquito relies on gametocytes, highly specialized sexual-stage parasites, that once mature, circulate in the peripheral vasculature of the human host...
May 16, 2016: Human Vaccines & Immunotherapeutics
A M Blagborough, K Musiychuk, H Bi, R M Jones, J A Chichester, S Streatfield, K A Sala, S E Zakutansky, L M Upton, R E Sinden, I Brian, S Biswas, J Sattabonkot, V Yusibov
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...
June 14, 2016: Vaccine
Kristen M Merino, Geetha P Bansal, Nirbhay Kumar
Sexual stages of Plasmodium are critical for malaria transmission and stage-specific antigens are important targets for development of malaria transmission-blocking vaccines. Plasmodium falciparum gamete surface antigen (Pfs48/45) is important for male gamete fertility and is being pursued as a candidate vaccine antigen. Vaccine-induced transmission-blocking antibodies recognize reduction-sensitive conformational epitopes in Pfs48/45. Processing and presentation of such disulphide-bond-constrained epitopes is critical for eliciting the desired immune responses...
August 2016: Immunology
Xu Kou, Wenqi Zheng, Feng Du, Fei Liu, Meilian Wang, Qi Fan, Liwang Cui, Enjie Luo, Yaming Cao
BACKGROUND: Transmission-blocking vaccines (TBVs) are a promising strategy for malaria control and elimination. However, candidate TBV antigens are currently limited, highlighting the urgency of identifying new antigens for TBV development. METHODS: Using a combination of bioinformatic analysis and functional studies in the rodent malaria model Plasmodium berghei, we identified a conserved Plasmodium protein PbPH (PBANKA_041720) containing a pleckstrin homology (PH) domain...
2016: Parasites & Vectors
Fengwu Li, Viengngeun Bounkeua, Kenneth Pettersen, Joseph M Vinetz
BACKGROUND: Plasmodium invasion of the mosquito midgut is a population bottleneck in the parasite lifecycle. Interference with molecular mechanisms by which the ookinete invades the mosquito midgut is one potential approach to developing malaria transmission-blocking strategies. Plasmodium aspartic proteases are one such class of potential targets: plasmepsin IV (known to be present in the asexual stage food vacuole) was previously shown to be involved in Plasmodium gallinaceum infection of the mosquito midgut, and plasmepsins VII and plasmepsin X (not known to be present in the asexual stage food vacuole) are upregulated in Plasmodium falciparum mosquito stages...
2016: Malaria Journal
Martijn W Vos, Will J R Stone, Karin M Koolen, Geert-Jan van Gemert, Ben van Schaijk, Didier Leroy, Robert W Sauerwein, Teun Bousema, Koen J Dechering
Current first-line treatments for uncomplicated falciparum malaria rapidly clear the asexual stages of the parasite, but do not fully prevent parasite transmission by mosquitoes. The standard membrane feeding assay (SMFA) is the biological gold standard assessment of transmission reducing activity (TRA), but its throughput is limited by the need to determine mosquito infection status by dissection and microscopy. Here we present a novel dissection-free luminescence based SMFA format using a transgenic Plasmodium falciparum reporter parasite without resistance to known antimalarials and therefore unrestricted in its utility in compound screening...
2015: Scientific Reports
Leonardo Lucantoni, Francesco Silvestrini, Michele Signore, Giulia Siciliano, Maarten Eldering, Koen J Dechering, Vicky M Avery, Pietro Alano
Plasmodium falciparum gametocytes, specifically the mature stages, are the only malaria parasite stage in humans transmissible to the mosquito vector. Anti-malarial drugs capable of killing these forms are considered essential for the eradication of malaria and tools allowing the screening of large compound libraries with high predictive power are needed to identify new candidates. As gametocytes are not a replicative stage it is difficult to apply the same drug screening methods used for asexual stages. Here we propose an assay, based on high content imaging, combining "classic" gametocyte viability readout based on gametocyte counts with a functional viability readout, based on gametocyte activation and the discrimination of the typical gamete spherical morphology...
2015: Scientific Reports
Watcharakorn Mongkol, Uraiwan Arunyawat, Wunrada Surat, Anchanee Kubera
Malaria transmission-blocking compounds have been studied to block the transmission of malaria parasites, especially the drug-resistant Plasmodium. Carboxypeptidase B (CPB) in the midgut of Anopheline mosquitoes has been demonstrated to be essential for the sexual development of Plasmodium in the mosquito. Thus, the CPB is a potential target for blocking compounds. The aim of this research was to screen compounds from the National Cancer Institute (NCI) diversity dataset and U.S. Food and Drug Administration (FDA)-approved drugs that could reduce the Anopheles CPB activity...
November 2015: Journal of Medical Entomology
Rajesh Kumar, Paresh C Ray, Dibyadyuti Datta, Geetha P Bansal, Evelina Angov, Nirbhay Kumar
Malaria transmission-blocking vaccines (TBV) targeting sexual stages of the parasite represent an ideal intervention to reduce the burden of the disease and eventual elimination at the population level in endemic regions. Immune responses against sexual stage antigens impair the development of parasite inside the mosquitoes. Target antigens identified in Plasmodium falciparum include surface proteins Pfs230 and Pfs48/45 in male and female gametocytes and Pfs25 expressed in zygotes and ookinetes. The latter has undergone extensive evaluation in pre-clinical and phase I clinical trials and remains one of the leading target antigens for the development of TBV...
September 22, 2015: Vaccine
Dibyadyuti Datta, Geetha P Bansal, Rajesh Kumar, Barry Ellefsen, Drew Hannaman, Nirbhay Kumar
Plasmodium falciparum sexual stage surface antigen Pfs25 is a well-established candidate for malaria transmission-blocking vaccine development. Immunization with DNA vaccines encoding Pfs25 has been shown to elicit potent antibody responses in mice and nonhuman primates. Studies aimed at further optimization have revealed improved immunogenicity through the application of in vivo electroporation and by using a heterologous prime-boost approach. The goal of the studies reported here was to systematically evaluate the impact of codon optimization, in vivo electroporation, and N-linked glycosylation on the immunogenicity of Pfs25 encoded by DNA vaccines...
September 2015: Clinical and Vaccine Immunology: CVI
Rajesh Kumar, Grace Ledet, Richard Graves, Dibyadyuti Datta, Shana Robinson, Geetha P Bansal, Tarun Mandal, Nirbhay Kumar
PURPOSE: To evaluate functional immunogenicity of CHrPfs25. a malaria transmission blocking vaccine antigen, using nanoemulsion and porous polymeric PLGA nanoparticles. METHODS: CHrPfs25 was formulated with nanoemulsions (NE) and poly(D,L-lactide-co-glycolide) nanoparticles (PLGA-NP) and evaluated via IM route in mice. Transmission blocking efficacy of antibodies was evaluated by standard mosquito membrane feeding assay using purified IgG from immune sera. Physicochemical properties and stability of various formulations were evaluated by measuring poly-dispersity index, particle size and zeta potential...
December 2015: Pharmaceutical Research
Sarah C Atkinson, Jennifer S Armistead, Derrick K Mathias, Maurice M Sandeu, Dingyin Tao, Nahid Borhani-Dizaji, Brian B Tarimo, Isabelle Morlais, Rhoel R Dinglasan, Natalie A Borg
Mosquito-based malaria transmission-blocking vaccines (mTBVs) target midgut-surface antigens of the Plasmodium parasite's obligate vector, the Anopheles mosquito. The alanyl aminopeptidase N (AnAPN1) is the leading mTBV immunogen; however, AnAPN1's role in Plasmodium infection of the mosquito and how anti-AnAPN1 antibodies functionally block parasite transmission have remained elusive. Here we present the 2.65-Å crystal structure of AnAPN1 and the immunoreactivity and transmission-blocking profiles of three monoclonal antibodies (mAbs) to AnAPN1, including mAb 4H5B7, which effectively blocks transmission of natural strains of Plasmodium falciparum...
July 2015: Nature Structural & Molecular Biology
M C Kapulu, D F Da, K Miura, Y Li, A M Blagborough, T S Churcher, D Nikolaeva, A R Williams, A L Goodman, I Sangare, A V Turner, M G Cottingham, A Nicosia, U Straschil, T Tsuboi, S C Gilbert, Carole A Long, R E Sinden, S J Draper, A V S Hill, A Cohuet, S Biswas
Malaria transmission-blocking vaccines (TBVs) target the development of Plasmodium parasites within the mosquito, with the aim of preventing malaria transmission from one infected individual to another. Different vaccine platforms, mainly protein-in-adjuvant formulations delivering the leading candidate antigens, have been developed independently and have reported varied transmission-blocking activities (TBA). Here, recombinant chimpanzee adenovirus 63, ChAd63, and modified vaccinia virus Ankara, MVA, expressing AgAPN1, Pfs230-C, Pfs25, and Pfs48/45 were generated...
2015: Scientific Reports
Yimin Wu, Robert E Sinden, Thomas S Churcher, Takafumi Tsuboi, Vidadi Yusibov
Despite decades of effort battling against malaria, the disease is still a major cause of morbidity and mortality. Transmission-blocking vaccines (TBVs) that target sexual stage parasite development could be an integral part of measures for malaria elimination. In the 1950s, Huff et al. first demonstrated the induction of transmission-blocking immunity in chickens by repeated immunizations with Plasmodium gallinaceum-infected red blood cells. Since then, significant progress has been made in identification of parasite antigens responsible for transmission-blocking activity...
June 2015: Advances in Parasitology
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