The Experts below are selected from a list of 300 Experts worldwide ranked by ideXlab platform
Shaden Kamhawi - One of the best experts on this subject based on the ideXlab platform.
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pre clinical antigenicity studies of an innovative multivalent Vaccine for human visceral Leishmaniasis
PLOS Neglected Tropical Diseases, 2017Co-Authors: Pedro Cecilio, Rhea N. Coler, Steven G Reed, Begona Perezcabezas, Laura Fernandez, Javier Moreno, Eugenia Carrillo, Jose M Requena, Epifanio Fichera, Shaden KamhawiAbstract:The notion that previous infection by Leishmania spp. in endemic areas leads to robust anti-Leishmania immunity, supports vaccination as a potentially effective approach to prevent disease development. Nevertheless, to date there is no Vaccine available for human Leishmaniasis. We optimized and assessed in vivo the safety and immunogenicity of an innovative Vaccine candidate against human visceral Leishmaniasis (VL), consisting of Virus-Like Particles (VLP) loaded with three different recombinant proteins (LJL143 from Lutzomyia longipalpis saliva as the vector-derived (VD) component, and KMP11 and LeishF3+, as parasite-derived (PD) antigens) and adjuvanted with GLA-SE, a TLR4 agonist. No apparent adverse reactions were observed during the experimental time-frame, which together with the normal hematological parameters detected seems to point to the safety of the formulation. Furthermore, measurements of antigen-specific cellular and humoral responses, generally higher in immunized versus control groups, confirmed the immunogenicity of the Vaccine formulation. Interestingly, the immune responses against the VD protein were reproducibly more robust than those elicited against Leishmanial antigens, and were apparently not caused by immunodominance of the VD antigen. Remarkably, priming with the VD protein alone and boosting with the complete Vaccine candidate contributed towards an increase of the immune responses to the PD antigens, assessed in the form of increased ex vivo CD4+ and CD8+ T cell proliferation against both the PD antigens and total Leishmania antigen (TLA). Overall, our immunogenicity data indicate that this innovative Vaccine formulation represents a promising anti-Leishmania Vaccine whose efficacy deserves to be tested in the context of the “natural infection”.
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Leishmania Vaccine development exploiting the host vector parasite interface
Expert Review of Vaccines, 2016Co-Authors: Steve Reed, Rhea N. Coler, D Mondal, Shaden Kamhawi, Jesus G ValenzuelaAbstract:Visceral Leishmaniasis (VL) is a disease transmitted by phlebotomine sand flies, fatal if untreated, and with no available human Vaccine. In rodents, cellular immunity to Leishmania parasite proteins as well as salivary proteins of the sand fly is associated with protection, making them worthy targets for further exploration as Vaccines. This review discusses the notion that a combination Vaccine including Leishmania and vector salivary antigens may improve Vaccine efficacy by targeting the parasite at its most vulnerable stage just after transmission. Furthermore, we put forward the notion that better modeling of natural transmission is needed to test efficacy of Vaccines. For example, the fact that individuals living in endemic areas are exposed to sand fly bites and will mount an immune response to salivary proteins should be considered in pre-clinical and clinical evaluation of Leishmaniasis Vaccines. Nevertheless, despite remaining obstacles there is good reason to be optimistic that safe and effective Vaccines against Leishmaniasis can be developed.
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Leishmania Vaccine development: exploiting the host–vector–parasite interface
Expert review of vaccines, 2015Co-Authors: Steve Reed, Rhea N. Coler, D Mondal, Shaden Kamhawi, Jesus G ValenzuelaAbstract:Visceral Leishmaniasis (VL) is a disease transmitted by phlebotomine sand flies, fatal if untreated, and with no available human Vaccine. In rodents, cellular immunity to Leishmania parasite proteins as well as salivary proteins of the sand fly is associated with protection, making them worthy targets for further exploration as Vaccines. This review discusses the notion that a combination Vaccine including Leishmania and vector salivary antigens may improve Vaccine efficacy by targeting the parasite at its most vulnerable stage just after transmission. Furthermore, we put forward the notion that better modeling of natural transmission is needed to test efficacy of Vaccines. For example, the fact that individuals living in endemic areas are exposed to sand fly bites and will mount an immune response to salivary proteins should be considered in pre-clinical and clinical evaluation of Leishmaniasis Vaccines. Nevertheless, despite remaining obstacles there is good reason to be optimistic that safe and effective Vaccines against Leishmaniasis can be developed.
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sand fly salivary proteins induce strong cellular immunity in a natural reservoir of visceral Leishmaniasis with adverse consequences for Leishmania
PLOS Pathogens, 2009Co-Authors: Nicolas Collin, Jesus G Valenzuela, Regis Gomes, Clarissa Teixeira, Lily I Cheng, Andre Laughinghouse, Jerrold M Ward, Dia Eldin Elnaiem, Laurent Fischer, Shaden KamhawiAbstract:Immunity to a sand fly salivary protein protects against visceral Leishmaniasis (VL) in hamsters. This protection was associated with the development of cellular immunity in the form of a delayed-type hypersensitivity response and the presence of IFN-γ at the site of sand fly bites. To date, there are no data available regarding the cellular immune response to sand fly saliva in dogs, the main reservoirs of VL in Latin America, and its role in protection from this fatal disease. Two of 35 salivary proteins from the vector sand fly Lutzomyia longipalpis, identified using a novel approach termed reverse antigen screening, elicited strong cellular immunity in dogs. Immunization with either molecule induced high IgG2 antibody levels and significant IFN-γ production following in vitro stimulation of PBMC with salivary gland homogenate (SGH). Upon challenge with uninfected or infected flies, immunized dogs developed a cellular response at the bite site characterized by lymphocytic infiltration and IFN-γ and IL-12 expression. Additionally, SGH-stimulated lymphocytes from immunized dogs efficiently killed Leishmania infantum chagasi within autologous macrophages. Certain sand fly salivary proteins are potent immunogens obligatorily co-deposited with Leishmania parasites during transmission. Their inclusion in an anti-Leishmania Vaccine would exploit anti-saliva immunity following an infective sand fly bite and set the stage for a protective anti-Leishmania immune response.
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Comparative salivary gland transcriptomics of sandfly vectors of visceral Leishmaniasis
BMC Genomics, 2006Co-Authors: Jennifer M Anderson, Fabiano Oliveira, Shaden Kamhawi, Mark Garfield, Ben J Mans, David Reynoso, Amy E Seitz, Phillip Lawyer, Myvan Pham, Jesus G ValenzuelaAbstract:Background Immune responses to sandfly saliva have been shown to protect animals against Leishmania infection. Yet very little is known about the molecular characteristics of salivary proteins from different sandflies, particularly from vectors transmitting visceral Leishmaniasis, the fatal form of the disease. Further knowledge of the repertoire of these salivary proteins will give us insights into the molecular evolution of these proteins and will help us select relevant antigens for the development of a vector based anti- Leishmania Vaccine. Results Two salivary gland cDNA libraries from female sandflies Phlebotomus argentipes and P. perniciosus were constructed, sequenced and proteomic analysis of the salivary proteins was performed. The majority of the sequenced transcripts from the two cDNA libraries coded for secreted proteins. In this analysis we identified transcripts coding for protein families not previously described in sandflies. A comparative sandfly salivary transcriptome analysis was performed by using these two cDNA libraries and two other sandfly salivary gland cDNA libraries from P. ariasi and Lutzomyia longipalpis , also vectors of visceral Leishmaniasis. Full-length secreted proteins from each sandfly library were compared using a stand-alone version of BLAST, creating formatted protein databases of each sandfly library. Related groups of proteins from each sandfly species were combined into defined families of proteins. With this comparison, we identified families of salivary proteins common among all of the sandflies studied, proteins to be genus specific and proteins that appear to be species specific. The common proteins included apyrase, yellow-related protein, antigen-5, PpSP15 and PpSP32-related protein, a 33-kDa protein, D7-related protein, a 39- and a 16.1- kDa protein and an endonuclease-like protein. Some of these families contained multiple members, including PPSP15-like, yellow proteins and D7-related proteins suggesting gene expansion in these proteins. Conclusion This comprehensive analysis allows us the identification of genus- specific proteins, species-specific proteins and, more importantly, proteins common among these different sandflies. These results give us insights into the repertoire of salivary proteins that are potential candidates for a vector-based Vaccine.
Jesus G Valenzuela - One of the best experts on this subject based on the ideXlab platform.
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engineering a vector based pan Leishmania Vaccine for humans proof of principle
Scientific Reports, 2020Co-Authors: Pedro Cecilio, James Oristian, Claudio Meneses, Tiago D Serafim, Jesus G Valenzuela, Anabela Cordeiro Da Silva, Fabiano OliveiraAbstract:Leishmaniasis is a spectrum of diseases transmitted by sand fly vectors that deposit Leishmania spp. parasites in the host skin during blood feeding. Currently, available treatment options are limited, associated with high toxicity and emerging resistance. Even though a Vaccine for human Leishmaniasis is considered an achievable goal, to date we still do not have one available, a consequence (amongst other factors) of a lack of pre-clinical to clinical translatability. Pre-exposure to uninfected sand fly bites or immunization with defined sand fly salivary proteins was shown to negatively impact infection. Still, cross-protection reports are rare and dependent on the phylogenetic proximity of the sand fly species, meaning that the applicability of a sand fly saliva-based Vaccine will be limited to a defined geography, one parasite species and one form of Leishmaniasis. As a proof of principle of a future vector saliva-based pan-Leishmania Vaccine, we engineered through a reverse vaccinology approach that maximizes translation to humans, a fusion protein consisting of immunogenic portions of PdSP15 and LJL143, sand fly salivary proteins demonstrated as potential Vaccine candidates against cutaneous and visceral Leishmaniasis, respectively. The in silico analysis was validated ex vivo, through T cell proliferation experiments, proving that the fusion protein (administered as a DNA Vaccine) maintained the immunogenicity of both PdSP15 and LJL143. Additionally, while no significant effect was detected in the context of L. major transmission by P. duboscqi, this DNA Vaccine was defined as partially protective, in the context of L. major transmission by L. longipalpis sand flies. Importantly, a high IFNγ response alone was not enough to confer protection, that mainly correlated with low T cell mediated Leishmania-specific IL-4 and IL-10 responses, and consequently with high pro/anti-inflammatory cytokine ratios. Overall our immunogenicity data suggests that to design a potentially safe vector-based pan-Leishmania Vaccine, without geographic restrictions and against all forms of Leishmaniasis is an achievable goal. This is why we propose our approach as a proof-of principle, perhaps not only applicable to the anti-Leishmania vector-based Vaccines' field, but also to other branches of knowledge that require the design of multi-epitope T cell Vaccines with a higher potential for translation.
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immunity to lulohya and lundep the salivary spreading factors from lutzomyia longipalpis protects against Leishmania major infection
PLOS Pathogens, 2018Co-Authors: Ines Martinmartin, Jesus G Valenzuela, Fabiano Oliveira, Andrezza C Chagas, Anderson B Guimaraescosta, Ian N Moore, Thiago Desouzavieira, Elda E Sanchez, Montamas Suntravat, Jose M C RibeiroAbstract:Salivary components from disease vectors help arthropods to acquire blood and have been shown to enhance pathogen transmission in different model systems. Here we show that two salivary enzymes from Lutzomyia longipalpis have a synergist effect that facilitates a more efficient blood meal intake and diffusion of other sialome components. We have previously shown that Lundep, a highly active endonuclease, enhances parasite infection and prevent blood clotting by inhibiting the intrinsic pathway of coagulation. To investigate the physiological role of a salivary hyaluronidase in blood feeding we cloned and expressed a recombinant hyaluronidase from Lu. longipalpis. Recombinant hyaluronidase (LuloHya) was expressed in mammalian cells and biochemically characterized in vitro. Our study showed that expression of neutrophil CXC chemokines and colony stimulating factors were upregulated in HMVEC cells after incubation with LuloHya and Lundep. These results were confirmed by the acute hemorrhage, edema and inflammation in a dermal necrosis (dermonecrotic) assay involving a massive infiltration of leukocytes, especially neutrophils, in mice co-injected with hemorrhagic factor and these two salivary proteins. Moreover, flow cytometry results showed that LuloHya and Lundep promote neutrophil recruitment to the bite site that may serve as a vehicle for establishment of Leishmania infection. A vaccination experiment demonstrated that LuloHya and Lundep confer protective immunity against cutaneous Leishmaniasis using the Lu. longipalpis—Leishmania major combination as a model. Animals (C57BL/6) immunized with LuloHya or Lundep showed minimal skin damage while lesions in control animals remained ulcerated. This protective immunity was abrogated when B-cell-deficient mice were used indicating that antibodies against both proteins play a significant role for disease protection. Rabbit-raised anti-LuloHya antibodies completely abrogated hyaluronidase activity in vitro. Moreover, in vivo experiments demonstrated that blocking LuloHya with specific antibodies interferes with sand fly blood feeding. This work highlights the relevance of vector salivary components in blood feeding and parasite transmission and further suggests the inclusion of these salivary proteins as components for an anti-Leishmania Vaccine.
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Leishmania Vaccine development exploiting the host vector parasite interface
Expert Review of Vaccines, 2016Co-Authors: Steve Reed, Rhea N. Coler, D Mondal, Shaden Kamhawi, Jesus G ValenzuelaAbstract:Visceral Leishmaniasis (VL) is a disease transmitted by phlebotomine sand flies, fatal if untreated, and with no available human Vaccine. In rodents, cellular immunity to Leishmania parasite proteins as well as salivary proteins of the sand fly is associated with protection, making them worthy targets for further exploration as Vaccines. This review discusses the notion that a combination Vaccine including Leishmania and vector salivary antigens may improve Vaccine efficacy by targeting the parasite at its most vulnerable stage just after transmission. Furthermore, we put forward the notion that better modeling of natural transmission is needed to test efficacy of Vaccines. For example, the fact that individuals living in endemic areas are exposed to sand fly bites and will mount an immune response to salivary proteins should be considered in pre-clinical and clinical evaluation of Leishmaniasis Vaccines. Nevertheless, despite remaining obstacles there is good reason to be optimistic that safe and effective Vaccines against Leishmaniasis can be developed.
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Leishmania Vaccine development: exploiting the host–vector–parasite interface
Expert review of vaccines, 2015Co-Authors: Steve Reed, Rhea N. Coler, D Mondal, Shaden Kamhawi, Jesus G ValenzuelaAbstract:Visceral Leishmaniasis (VL) is a disease transmitted by phlebotomine sand flies, fatal if untreated, and with no available human Vaccine. In rodents, cellular immunity to Leishmania parasite proteins as well as salivary proteins of the sand fly is associated with protection, making them worthy targets for further exploration as Vaccines. This review discusses the notion that a combination Vaccine including Leishmania and vector salivary antigens may improve Vaccine efficacy by targeting the parasite at its most vulnerable stage just after transmission. Furthermore, we put forward the notion that better modeling of natural transmission is needed to test efficacy of Vaccines. For example, the fact that individuals living in endemic areas are exposed to sand fly bites and will mount an immune response to salivary proteins should be considered in pre-clinical and clinical evaluation of Leishmaniasis Vaccines. Nevertheless, despite remaining obstacles there is good reason to be optimistic that safe and effective Vaccines against Leishmaniasis can be developed.
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sand fly salivary proteins induce strong cellular immunity in a natural reservoir of visceral Leishmaniasis with adverse consequences for Leishmania
PLOS Pathogens, 2009Co-Authors: Nicolas Collin, Jesus G Valenzuela, Regis Gomes, Clarissa Teixeira, Lily I Cheng, Andre Laughinghouse, Jerrold M Ward, Dia Eldin Elnaiem, Laurent Fischer, Shaden KamhawiAbstract:Immunity to a sand fly salivary protein protects against visceral Leishmaniasis (VL) in hamsters. This protection was associated with the development of cellular immunity in the form of a delayed-type hypersensitivity response and the presence of IFN-γ at the site of sand fly bites. To date, there are no data available regarding the cellular immune response to sand fly saliva in dogs, the main reservoirs of VL in Latin America, and its role in protection from this fatal disease. Two of 35 salivary proteins from the vector sand fly Lutzomyia longipalpis, identified using a novel approach termed reverse antigen screening, elicited strong cellular immunity in dogs. Immunization with either molecule induced high IgG2 antibody levels and significant IFN-γ production following in vitro stimulation of PBMC with salivary gland homogenate (SGH). Upon challenge with uninfected or infected flies, immunized dogs developed a cellular response at the bite site characterized by lymphocytic infiltration and IFN-γ and IL-12 expression. Additionally, SGH-stimulated lymphocytes from immunized dogs efficiently killed Leishmania infantum chagasi within autologous macrophages. Certain sand fly salivary proteins are potent immunogens obligatorily co-deposited with Leishmania parasites during transmission. Their inclusion in an anti-Leishmania Vaccine would exploit anti-saliva immunity following an infective sand fly bite and set the stage for a protective anti-Leishmania immune response.
Angela J. Toepp - One of the best experts on this subject based on the ideXlab platform.
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Randomized, controlled, double-blinded field trial to assess Leishmania Vaccine effectiveness as immunotherapy for canine leishmaniosis
Vaccine, 2018Co-Authors: Angela J. Toepp, Mandy Larson, Geneva Wilson, Tara Grinnage-pulley, Carolyne Bennett, Adam Leal-lima, Bryan Anderson, Molly Parrish, Michael G. Anderson, Hailie FowlerAbstract:Abstract Better tools are necessary to eliminate visceral Leishmaniasis (VL). Modeling studies for regional Leishmania elimination indicate that an effective Vaccine is a critical tool. Dogs are the reservoir host of L. infantum in Brazil and the Mediterranean basin, and therefore are an important target for public health interventions as well as a relevant disease model for human VL. No Vaccine has been efficacious as an immunotherapy to prevent progression of already diagnostically positive individuals to symptomatic Leishmaniasis. We performed a double-blinded, block-randomized, placebo-controlled, Vaccine immunotherapy trial testing the efficacy of a recombinant Leishmania A2 protein, saponin-adjuvanted, Vaccine, LeishTec®, in owned hunting dogs infected with L. infantum. The primary outcome was reduction of clinical progression, with reduction of mortality as a secondary outcome. Vaccination as an immunotherapy reduced the risk of progression to clinically overt Leishmaniasis by 25% in asymptomatic dogs (RR: 1.33 95% C.I. 1.009–1.786 p-value: 0.0450). Receiving Vaccine vs. placebo reduced all-cause mortality in younger asymptomatic dogs by 70% (RR: 3.19 95% C.I.: 1.185–8.502 p-value = 0.0245). Vaccination of infected-healthy animals with an anti-Leishmania Vaccine significantly reduced clinical progression and decreased all-cause mortality. Use of vaccination in infected-healthy dogs can be a tool for Leishmania control.
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safety analysis of Leishmania Vaccine used in a randomized canine Vaccine immunotherapy trial
American Journal of Tropical Medicine and Hygiene, 2018Co-Authors: Angela J. Toepp, Mandy Larson, Geneva Wilson, Carolyne Bennett, Molly Parrish, Michael G. Anderson, Hailie Fowler, Tara Grinnagepulley, Katherine Gibsoncorely, Radhika GharpureAbstract:In Leishmania infantum-endemic countries, controlling infection within dogs, the domestic reservoir, is critical to public health. There is a need for safe Vaccines that prevent canine progression with disease and transmission to others. Protective vaccination against Leishmania requires mounting a strong, inflammatory, Type 1 response. Three commercially available canine Vaccines on the global veterinary market use saponin or inflammatory antigen components (Letifend) as a strong pro-inflammatory adjuvant. There is very little information detailing safety of saponin as an adjuvant in field trials. Safety analyses for the use of Vaccine as an immunotherapeutic in asymptomatically infected animals are completely lacking. Leishmania infantum, the causative agent of canine Leishmaniasis, is enzootic within U.S. hunting hounds. We assessed the safety of LeishTec® after use in dogs from two different clinical states: 1) without clinical signs and tested negative on polymerase chain reaction and serology or 2) without clinical signs and positive for at least one Leishmania diagnostic test. Vaccine safety was assessed after all three vaccinations to quantify the number and severity of adverse events. Vaccinated animals had an adverse event rate of 3.09%, whereas placebo animals had 0.68%. Receiving Vaccine was correlated with the occurrence of mild, site-specific, reactions. Occurrence of severe adverse events was not associated with having received Vaccine. Infected, asymptomatic animals did not have a higher rate of adverse events. Use of vaccination is, therefore, likely to be safe in infected, asymptomatic animals.
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Safety Analysis of Leishmania Vaccine Used in a Randomized Canine Vaccine/Immunotherapy Trial.
The American journal of tropical medicine and hygiene, 2018Co-Authors: Angela J. Toepp, Mandy Larson, Geneva Wilson, Tara Grinnage-pulley, Carolyne Bennett, Molly Parrish, Michael G. Anderson, Hailie Fowler, Katherine Gibson-corely, Radhika GharpureAbstract:In Leishmania infantum-endemic countries, controlling infection within dogs, the domestic reservoir, is critical to public health. There is a need for safe Vaccines that prevent canine progression with disease and transmission to others. Protective vaccination against Leishmania requires mounting a strong, inflammatory, Type 1 response. Three commercially available canine Vaccines on the global veterinary market use saponin or inflammatory antigen components (Letifend) as a strong pro-inflammatory adjuvant. There is very little information detailing safety of saponin as an adjuvant in field trials. Safety analyses for the use of Vaccine as an immunotherapeutic in asymptomatically infected animals are completely lacking. Leishmania infantum, the causative agent of canine Leishmaniasis, is enzootic within U.S. hunting hounds. We assessed the safety of LeishTec® after use in dogs from two different clinical states: 1) without clinical signs and tested negative on polymerase chain reaction and serology or 2) without clinical signs and positive for at least one Leishmania diagnostic test. Vaccine safety was assessed after all three vaccinations to quantify the number and severity of adverse events. Vaccinated animals had an adverse event rate of 3.09%, whereas placebo animals had 0.68%. Receiving Vaccine was correlated with the occurrence of mild, site-specific, reactions. Occurrence of severe adverse events was not associated with having received Vaccine. Infected, asymptomatic animals did not have a higher rate of adverse events. Use of vaccination is, therefore, likely to be safe in infected, asymptomatic animals.
Hailie Fowler - One of the best experts on this subject based on the ideXlab platform.
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Randomized, controlled, double-blinded field trial to assess Leishmania Vaccine effectiveness as immunotherapy for canine leishmaniosis
Vaccine, 2018Co-Authors: Angela J. Toepp, Mandy Larson, Geneva Wilson, Tara Grinnage-pulley, Carolyne Bennett, Adam Leal-lima, Bryan Anderson, Molly Parrish, Michael G. Anderson, Hailie FowlerAbstract:Abstract Better tools are necessary to eliminate visceral Leishmaniasis (VL). Modeling studies for regional Leishmania elimination indicate that an effective Vaccine is a critical tool. Dogs are the reservoir host of L. infantum in Brazil and the Mediterranean basin, and therefore are an important target for public health interventions as well as a relevant disease model for human VL. No Vaccine has been efficacious as an immunotherapy to prevent progression of already diagnostically positive individuals to symptomatic Leishmaniasis. We performed a double-blinded, block-randomized, placebo-controlled, Vaccine immunotherapy trial testing the efficacy of a recombinant Leishmania A2 protein, saponin-adjuvanted, Vaccine, LeishTec®, in owned hunting dogs infected with L. infantum. The primary outcome was reduction of clinical progression, with reduction of mortality as a secondary outcome. Vaccination as an immunotherapy reduced the risk of progression to clinically overt Leishmaniasis by 25% in asymptomatic dogs (RR: 1.33 95% C.I. 1.009–1.786 p-value: 0.0450). Receiving Vaccine vs. placebo reduced all-cause mortality in younger asymptomatic dogs by 70% (RR: 3.19 95% C.I.: 1.185–8.502 p-value = 0.0245). Vaccination of infected-healthy animals with an anti-Leishmania Vaccine significantly reduced clinical progression and decreased all-cause mortality. Use of vaccination in infected-healthy dogs can be a tool for Leishmania control.
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safety analysis of Leishmania Vaccine used in a randomized canine Vaccine immunotherapy trial
American Journal of Tropical Medicine and Hygiene, 2018Co-Authors: Angela J. Toepp, Mandy Larson, Geneva Wilson, Carolyne Bennett, Molly Parrish, Michael G. Anderson, Hailie Fowler, Tara Grinnagepulley, Katherine Gibsoncorely, Radhika GharpureAbstract:In Leishmania infantum-endemic countries, controlling infection within dogs, the domestic reservoir, is critical to public health. There is a need for safe Vaccines that prevent canine progression with disease and transmission to others. Protective vaccination against Leishmania requires mounting a strong, inflammatory, Type 1 response. Three commercially available canine Vaccines on the global veterinary market use saponin or inflammatory antigen components (Letifend) as a strong pro-inflammatory adjuvant. There is very little information detailing safety of saponin as an adjuvant in field trials. Safety analyses for the use of Vaccine as an immunotherapeutic in asymptomatically infected animals are completely lacking. Leishmania infantum, the causative agent of canine Leishmaniasis, is enzootic within U.S. hunting hounds. We assessed the safety of LeishTec® after use in dogs from two different clinical states: 1) without clinical signs and tested negative on polymerase chain reaction and serology or 2) without clinical signs and positive for at least one Leishmania diagnostic test. Vaccine safety was assessed after all three vaccinations to quantify the number and severity of adverse events. Vaccinated animals had an adverse event rate of 3.09%, whereas placebo animals had 0.68%. Receiving Vaccine was correlated with the occurrence of mild, site-specific, reactions. Occurrence of severe adverse events was not associated with having received Vaccine. Infected, asymptomatic animals did not have a higher rate of adverse events. Use of vaccination is, therefore, likely to be safe in infected, asymptomatic animals.
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Safety Analysis of Leishmania Vaccine Used in a Randomized Canine Vaccine/Immunotherapy Trial.
The American journal of tropical medicine and hygiene, 2018Co-Authors: Angela J. Toepp, Mandy Larson, Geneva Wilson, Tara Grinnage-pulley, Carolyne Bennett, Molly Parrish, Michael G. Anderson, Hailie Fowler, Katherine Gibson-corely, Radhika GharpureAbstract:In Leishmania infantum-endemic countries, controlling infection within dogs, the domestic reservoir, is critical to public health. There is a need for safe Vaccines that prevent canine progression with disease and transmission to others. Protective vaccination against Leishmania requires mounting a strong, inflammatory, Type 1 response. Three commercially available canine Vaccines on the global veterinary market use saponin or inflammatory antigen components (Letifend) as a strong pro-inflammatory adjuvant. There is very little information detailing safety of saponin as an adjuvant in field trials. Safety analyses for the use of Vaccine as an immunotherapeutic in asymptomatically infected animals are completely lacking. Leishmania infantum, the causative agent of canine Leishmaniasis, is enzootic within U.S. hunting hounds. We assessed the safety of LeishTec® after use in dogs from two different clinical states: 1) without clinical signs and tested negative on polymerase chain reaction and serology or 2) without clinical signs and positive for at least one Leishmania diagnostic test. Vaccine safety was assessed after all three vaccinations to quantify the number and severity of adverse events. Vaccinated animals had an adverse event rate of 3.09%, whereas placebo animals had 0.68%. Receiving Vaccine was correlated with the occurrence of mild, site-specific, reactions. Occurrence of severe adverse events was not associated with having received Vaccine. Infected, asymptomatic animals did not have a higher rate of adverse events. Use of vaccination is, therefore, likely to be safe in infected, asymptomatic animals.
Radhika Gharpure - One of the best experts on this subject based on the ideXlab platform.
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safety analysis of Leishmania Vaccine used in a randomized canine Vaccine immunotherapy trial
American Journal of Tropical Medicine and Hygiene, 2018Co-Authors: Angela J. Toepp, Mandy Larson, Geneva Wilson, Carolyne Bennett, Molly Parrish, Michael G. Anderson, Hailie Fowler, Tara Grinnagepulley, Katherine Gibsoncorely, Radhika GharpureAbstract:In Leishmania infantum-endemic countries, controlling infection within dogs, the domestic reservoir, is critical to public health. There is a need for safe Vaccines that prevent canine progression with disease and transmission to others. Protective vaccination against Leishmania requires mounting a strong, inflammatory, Type 1 response. Three commercially available canine Vaccines on the global veterinary market use saponin or inflammatory antigen components (Letifend) as a strong pro-inflammatory adjuvant. There is very little information detailing safety of saponin as an adjuvant in field trials. Safety analyses for the use of Vaccine as an immunotherapeutic in asymptomatically infected animals are completely lacking. Leishmania infantum, the causative agent of canine Leishmaniasis, is enzootic within U.S. hunting hounds. We assessed the safety of LeishTec® after use in dogs from two different clinical states: 1) without clinical signs and tested negative on polymerase chain reaction and serology or 2) without clinical signs and positive for at least one Leishmania diagnostic test. Vaccine safety was assessed after all three vaccinations to quantify the number and severity of adverse events. Vaccinated animals had an adverse event rate of 3.09%, whereas placebo animals had 0.68%. Receiving Vaccine was correlated with the occurrence of mild, site-specific, reactions. Occurrence of severe adverse events was not associated with having received Vaccine. Infected, asymptomatic animals did not have a higher rate of adverse events. Use of vaccination is, therefore, likely to be safe in infected, asymptomatic animals.
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Safety Analysis of Leishmania Vaccine Used in a Randomized Canine Vaccine/Immunotherapy Trial.
The American journal of tropical medicine and hygiene, 2018Co-Authors: Angela J. Toepp, Mandy Larson, Geneva Wilson, Tara Grinnage-pulley, Carolyne Bennett, Molly Parrish, Michael G. Anderson, Hailie Fowler, Katherine Gibson-corely, Radhika GharpureAbstract:In Leishmania infantum-endemic countries, controlling infection within dogs, the domestic reservoir, is critical to public health. There is a need for safe Vaccines that prevent canine progression with disease and transmission to others. Protective vaccination against Leishmania requires mounting a strong, inflammatory, Type 1 response. Three commercially available canine Vaccines on the global veterinary market use saponin or inflammatory antigen components (Letifend) as a strong pro-inflammatory adjuvant. There is very little information detailing safety of saponin as an adjuvant in field trials. Safety analyses for the use of Vaccine as an immunotherapeutic in asymptomatically infected animals are completely lacking. Leishmania infantum, the causative agent of canine Leishmaniasis, is enzootic within U.S. hunting hounds. We assessed the safety of LeishTec® after use in dogs from two different clinical states: 1) without clinical signs and tested negative on polymerase chain reaction and serology or 2) without clinical signs and positive for at least one Leishmania diagnostic test. Vaccine safety was assessed after all three vaccinations to quantify the number and severity of adverse events. Vaccinated animals had an adverse event rate of 3.09%, whereas placebo animals had 0.68%. Receiving Vaccine was correlated with the occurrence of mild, site-specific, reactions. Occurrence of severe adverse events was not associated with having received Vaccine. Infected, asymptomatic animals did not have a higher rate of adverse events. Use of vaccination is, therefore, likely to be safe in infected, asymptomatic animals.