The Experts below are selected from a list of 30075 Experts worldwide ranked by ideXlab platform
Susheel K Singh - One of the best experts on this subject based on the ideXlab platform.
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pfs230 and pfs48 45 fusion proteins elicit strong transmission Blocking Antibody responses against plasmodium falciparum
Frontiers in Immunology, 2019Co-Authors: Susheel K Singh, Susan Thrane, Bishwanath Kumar Chourasia, Karina Teelen, Wouter Graumans, Rianne Stoter, Geertjan Van Gemert, Marga Van De Vegtebolmer, Morten A NielsenAbstract:The Plasmodium falciparum Pfs230 and Pfs48/45 proteins are expressed during transmission from man to mosquito and are leading candidates for a malaria transmission Blocking vaccine. Individually they generate transmission Blocking (TB) antibodies in rodent models. Whether the single protein vaccines are suitable to use in field settings will primarily depend on their potency to elicit functional antibodies. We hypothesized that a combination of both proteins will be more potent than each protein individually. Therefore we designed chimeric proteins composed of fragments of both Pfs230 and Pfs48/45 as well as single protein fragments, and expressed these in Lactoccus lactis. Both the individual Pfs230 and Pfs48/45 fragments and chimeras elicited high levels of functional antibodies in mice. Importantly, one of the chimeric proteins elicited over threefold higher transmission Blocking Antibody responses than the single antigens alone. Furthermore the immunogenicity of one of the chimeras could be enhanced through coupling to a virus-like particle (VLP). Altogether these data support further clinical development of these novel constructs.
Marga Van De Vegtebolmer - One of the best experts on this subject based on the ideXlab platform.
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pfs230 and pfs48 45 fusion proteins elicit strong transmission Blocking Antibody responses against plasmodium falciparum
Frontiers in Immunology, 2019Co-Authors: Susheel K Singh, Susan Thrane, Bishwanath Kumar Chourasia, Karina Teelen, Wouter Graumans, Rianne Stoter, Geertjan Van Gemert, Marga Van De Vegtebolmer, Morten A NielsenAbstract:The Plasmodium falciparum Pfs230 and Pfs48/45 proteins are expressed during transmission from man to mosquito and are leading candidates for a malaria transmission Blocking vaccine. Individually they generate transmission Blocking (TB) antibodies in rodent models. Whether the single protein vaccines are suitable to use in field settings will primarily depend on their potency to elicit functional antibodies. We hypothesized that a combination of both proteins will be more potent than each protein individually. Therefore we designed chimeric proteins composed of fragments of both Pfs230 and Pfs48/45 as well as single protein fragments, and expressed these in Lactoccus lactis. Both the individual Pfs230 and Pfs48/45 fragments and chimeras elicited high levels of functional antibodies in mice. Importantly, one of the chimeric proteins elicited over threefold higher transmission Blocking Antibody responses than the single antigens alone. Furthermore the immunogenicity of one of the chimeras could be enhanced through coupling to a virus-like particle (VLP). Altogether these data support further clinical development of these novel constructs.
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a novel plant produced pfs25 fusion subunit vaccine induces long lasting transmission Blocking Antibody responses
Human Vaccines & Immunotherapeutics, 2015Co-Authors: Mark R Jones, Marga Van De Vegtebolmer, Jessica A Chichester, Slobodanka D Manceva, Sandra K Gibbs, Konstantin Musiychuk, Moneim Shamloul, Joey Norikane, Stephen J Streatfield, Will RoeffenAbstract:Malaria transmission Blocking vaccines (TBV) directed against proteins expressed on sexual stages of Plasmodium falciparum in the mosquito midgut are considered an effective means to reduce malaria transmission. Antibodies induced by TBV block sporogonic development in the mosquito, and thus transmission to the next human host. The Pfs25 protein, expressed on the surface of gametes, zygotes and ookinetes, is one of the primary targets for TBV development. Using a plant virus-based transient expression system, we have successfully produced Pfs25 fused to a modified lichenase (LicKM) carrier in Nicotiana benthamiana, purified and characterized the protein (Pfs25-FhCMB), and evaluated this vaccine candidate in animal models for the induction of transmission Blocking antibodies. Soluble Pfs25-FhCMB was expressed in plants at a high level, and induced transmission Blocking antibodies that persisted for up to 6 months post immunization in mice and rabbits. These data demonstrate the potential of the new malaria...
Will Roeffen - One of the best experts on this subject based on the ideXlab platform.
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a novel plant produced pfs25 fusion subunit vaccine induces long lasting transmission Blocking Antibody responses
Human Vaccines & Immunotherapeutics, 2015Co-Authors: Mark R Jones, Marga Van De Vegtebolmer, Jessica A Chichester, Slobodanka D Manceva, Sandra K Gibbs, Konstantin Musiychuk, Moneim Shamloul, Joey Norikane, Stephen J Streatfield, Will RoeffenAbstract:Malaria transmission Blocking vaccines (TBV) directed against proteins expressed on sexual stages of Plasmodium falciparum in the mosquito midgut are considered an effective means to reduce malaria transmission. Antibodies induced by TBV block sporogonic development in the mosquito, and thus transmission to the next human host. The Pfs25 protein, expressed on the surface of gametes, zygotes and ookinetes, is one of the primary targets for TBV development. Using a plant virus-based transient expression system, we have successfully produced Pfs25 fused to a modified lichenase (LicKM) carrier in Nicotiana benthamiana, purified and characterized the protein (Pfs25-FhCMB), and evaluated this vaccine candidate in animal models for the induction of transmission Blocking antibodies. Soluble Pfs25-FhCMB was expressed in plants at a high level, and induced transmission Blocking antibodies that persisted for up to 6 months post immunization in mice and rabbits. These data demonstrate the potential of the new malaria...
Kazutoyo Miura - One of the best experts on this subject based on the ideXlab platform.
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identification of domains within pfs230 that elicit transmission Blocking Antibody responses
Vaccine, 2019Co-Authors: Mayumi Tachibana, Kazutoyo Miura, Eizo Takashima, Masayuki Morita, Hikaru Nagaoka, Luwen Zhou, Carole A Long, Richter C King, Motomi Torii, Takafumi TsuboiAbstract:Abstract A transmission-Blocking vaccine (TBV) against Plasmodium falciparum is likely to be a valuable tool in a malaria eradication program. Pfs230 is one of the major TBV candidates, and multiple Pfs230-based vaccines induced antibodies, which prevented oocyst formation in mosquitoes as determined by a standard membrane-feeding assay (SMFA). Pfs230 is a >300 kDa protein consisting of 14 cysteine motif (CM) domains, and the size and cysteine-rich nature of the molecule have hampered its production as an intact protein. Except for one early study with maltose-binding protein fusion Pfs230 constructs expressed in Esherichia coli, all other studies have focused on only the first four CM domains in the Pfs230 molecule. To identify all possible TBV candidate domains, we systematically produced either single-CM-domain (a total of 14), 2-CM-domain (7), or 4-CM-domain (6) recombinant protein fragments using a eukaryotic wheat germ cell-free expression system (WGCFS). In addition, two more constructs which covered previously published regions, and an N-terminal prodomain construct spanning the natural cleavage site of Pfs230 were produced. Antisera against each fragment were generated in mice and we evaluated the reactivity to native Pfs230 protein by Western blots and immunofluorescence assay (IFA), and functionality by SMFA. All 30 WGCFS-produced Pfs230 constructs were immunogenic in mice. Approximately half of the mouse antibodies specifically recognized native Pfs230 by Western blots with variable band intensities. Among them, seven antibodies showed higher reactivities against native Pfs230 determined by IFA. Interestingly, antibodies against all protein fragments containing CM domain 1 displayed strong inhibitions in SMFA, while antibodies generated using constructs without CM domain 1 showed no inhibition. The results strongly support the concept that future Pfs230-based vaccine development should focus on the Pfs230 CM domain 1.
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structural basis for recognition of the malaria vaccine candidate pfs48 45 by a transmission Blocking Antibody
Nature Communications, 2018Co-Authors: Frank Lennartz, Florian Brod, Rebecca A Dabbs, Kazutoyo Miura, D Mekhaiel, Arianna Marini, Matthijs M Jore, M M Sogaard, Thomas Jorgensen, W A De JonghAbstract:The quest to develop an effective malaria vaccine remains a major priority in the fight against global infectious disease. An approach with great potential is a transmission-Blocking vaccine which induces antibodies that prevent establishment of a productive infection in mosquitos that feed on infected humans, thereby stopping the transmission cycle. One of the most promising targets for such a vaccine is the gamete surface protein, Pfs48/45. Here we establish a system for production of full-length Pfs48/45 and use this to raise a panel of monoclonal antibodies. We map the binding regions of these antibodies on Pfs48/45 and correlate the location of their epitopes with their transmission-Blocking activity. Finally, we present the structure of the C-terminal domain of Pfs48/45 bound to the most potent transmission-Blocking Antibody, and provide key molecular information for future structure-guided immunogen design.
Rebecca S Bahn - One of the best experts on this subject based on the ideXlab platform.
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a stimulatory thyrotropin receptor Antibody enhances hyaluronic acid synthesis in graves orbital fibroblasts inhibition by an igf i receptor Blocking Antibody
The Journal of Clinical Endocrinology and Metabolism, 2012Co-Authors: Seema Kumar, Seethalakshmi Iyer, Hilary Bauer, Michael J Coenen, Rebecca S BahnAbstract:Context: Graves' ophthalmopathy (GO) is characterized by expanded volume of the orbital fat and extraocular muscle tissues and elevated levels of TSH receptor autoantibodies (TRAb). The expansion of orbital tissues involves accumulation of hyaluronic acid (HA) within the orbit. Objective: The objective of the study was to determine whether a monoclonal stimulatory TRAb (M22) impacts HA synthesis in GO orbital cells and, if so, whether this might be blocked by an IGF-I receptor (IGF-IR)-Blocking Antibody (1H7) or inhibitors of various downstream signaling cascades. Design: GO orbital fibroblast cultures (n = 6) were treated with M22, bovine TSH (bTSH), or IGF-I in serum-free medium. Some cultures also received 1H7, LY294002, rapamycin, or protein kinase A inhibitor. Main Outcome Measures: HA production and phosphorylated Akt levels in media or immunoblotting for phosphorylated Akt were measured. Results: M22 or bTSH stimulated HA synthesis (2.1-fold with 100 ng/ml M22 and 1.9-fold with 10 U/liter bTSH; P <...