The Experts below are selected from a list of 18744 Experts worldwide ranked by ideXlab platform
Brian R Murphy - One of the best experts on this subject based on the ideXlab platform.
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chimeric west nile dengue virus vaccine candidate Preclinical Evaluation in mice geese and monkeys for safety and immunogenicity
Vaccine, 2006Co-Authors: Alexander G Pletnev, David E Swayne, Jim Speicher, Alexander A Rumyantsev, Brian R MurphyAbstract:Abstract A live attenuated virus vaccine is being developed to protect against West Nile virus (WN) disease in humans. Previously, it was found that chimeric West Nile/dengue viruses (WN/DEN4 and WN/DEN4Δ30) bearing the membrane precursor and envelope protein genes of WN on a backbone of dengue type 4 virus (DEN4) with or without a deletion of 30 nucleotides (Δ30) in the 3′ noncoding region of the DEN4 part of the chimeric genome were attenuated and efficacious in mice and monkeys against WN challenge. Here, we report the generation of a clinical lot of WN/DEN4Δ30 virus and its further Preclinical Evaluation for safety and immunogenicity in mice, geese and monkeys. The vaccine candidate had lost neuroinvasiveness in highly sensitive immunodeficient mice inoculated intraperitoneally and had greatly reduced neurovirulence in suckling mice inoculated intracerebrally (IC). Compared to the wild-type WN parent, the chimeric virus was highly restricted in replication in both murine and human neuroblastoma cells as well as in brains of suckling mice. The WN/DEN4Δ30 virus failed to infect geese, indicating that chimerization of WN with DEN4 completely attenuated WN for this avian host. This observation suggests that the WN/DEN4 chimeric viruses would be restricted in their ability to be transmitted from vaccinees to domestic or wild birds. In monkeys, the WN/DEN4Δ30 vaccine candidate was highly immunogenic despite its low level of replication with undetectable viremia. Furthermore, the WN/DEN4Δ30 vaccine virus was safe and readily induced neutralizing antibodies against WN in monkeys immune to each of the four serotypes of dengue virus. These studies confirm the attenuation of WN/DEN4Δ30 for non-human primates, including dengue-immune monkeys, and demonstrate both a highly restricted replication (>10 8 -fold decrease) in the brain of mice inoculated IC and an absence of infectivity for birds, findings that indicate this vaccine should be safe for both the recipient and the environment.
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chimeric west nile dengue virus vaccine candidate Preclinical Evaluation in mice geese and monkeys for safety and immunogenicity
Vaccine, 2006Co-Authors: Alexander G Pletnev, David E Swayne, Jim Speicher, Alexander A Rumyantsev, Brian R MurphyAbstract:A live attenuated virus vaccine is being developed to protect against West Nile virus (WN) disease in humans. Previously, it was found that chimeric West Nile/dengue viruses (WN/DEN4 and WN/DEN4Delta30) bearing the membrane precursor and envelope protein genes of WN on a backbone of dengue type 4 virus (DEN4) with or without a deletion of 30 nucleotides (Delta30) in the 3' noncoding region of the DEN4 part of the chimeric genome were attenuated and efficacious in mice and monkeys against WN challenge. Here, we report the generation of a clinical lot of WN/DEN4Delta30 virus and its further Preclinical Evaluation for safety and immunogenicity in mice, geese and monkeys. The vaccine candidate had lost neuroinvasiveness in highly sensitive immunodeficient mice inoculated intraperitoneally and had greatly reduced neurovirulence in suckling mice inoculated intracerebrally (IC). Compared to the wild-type WN parent, the chimeric virus was highly restricted in replication in both murine and human neuroblastoma cells as well as in brains of suckling mice. The WN/DEN4Delta30 virus failed to infect geese, indicating that chimerization of WN with DEN4 completely attenuated WN for this avian host. This observation suggests that the WN/DEN4 chimeric viruses would be restricted in their ability to be transmitted from vaccinees to domestic or wild birds. In monkeys, the WN/DEN4Delta30 vaccine candidate was highly immunogenic despite its low level of replication with undetectable viremia. Furthermore, the WN/DEN4Delta30 vaccine virus was safe and readily induced neutralizing antibodies against WN in monkeys immune to each of the four serotypes of dengue virus. These studies confirm the attenuation of WN/DEN4Delta30 for non-human primates, including dengue-immune monkeys, and demonstrate both a highly restricted replication (>10(8)-fold decrease) in the brain of mice inoculated IC and an absence of infectivity for birds, findings that indicate this vaccine should be safe for both the recipient and the environment.
Alexander G Pletnev - One of the best experts on this subject based on the ideXlab platform.
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chimeric west nile dengue virus vaccine candidate Preclinical Evaluation in mice geese and monkeys for safety and immunogenicity
Vaccine, 2006Co-Authors: Alexander G Pletnev, David E Swayne, Jim Speicher, Alexander A Rumyantsev, Brian R MurphyAbstract:Abstract A live attenuated virus vaccine is being developed to protect against West Nile virus (WN) disease in humans. Previously, it was found that chimeric West Nile/dengue viruses (WN/DEN4 and WN/DEN4Δ30) bearing the membrane precursor and envelope protein genes of WN on a backbone of dengue type 4 virus (DEN4) with or without a deletion of 30 nucleotides (Δ30) in the 3′ noncoding region of the DEN4 part of the chimeric genome were attenuated and efficacious in mice and monkeys against WN challenge. Here, we report the generation of a clinical lot of WN/DEN4Δ30 virus and its further Preclinical Evaluation for safety and immunogenicity in mice, geese and monkeys. The vaccine candidate had lost neuroinvasiveness in highly sensitive immunodeficient mice inoculated intraperitoneally and had greatly reduced neurovirulence in suckling mice inoculated intracerebrally (IC). Compared to the wild-type WN parent, the chimeric virus was highly restricted in replication in both murine and human neuroblastoma cells as well as in brains of suckling mice. The WN/DEN4Δ30 virus failed to infect geese, indicating that chimerization of WN with DEN4 completely attenuated WN for this avian host. This observation suggests that the WN/DEN4 chimeric viruses would be restricted in their ability to be transmitted from vaccinees to domestic or wild birds. In monkeys, the WN/DEN4Δ30 vaccine candidate was highly immunogenic despite its low level of replication with undetectable viremia. Furthermore, the WN/DEN4Δ30 vaccine virus was safe and readily induced neutralizing antibodies against WN in monkeys immune to each of the four serotypes of dengue virus. These studies confirm the attenuation of WN/DEN4Δ30 for non-human primates, including dengue-immune monkeys, and demonstrate both a highly restricted replication (>10 8 -fold decrease) in the brain of mice inoculated IC and an absence of infectivity for birds, findings that indicate this vaccine should be safe for both the recipient and the environment.
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chimeric west nile dengue virus vaccine candidate Preclinical Evaluation in mice geese and monkeys for safety and immunogenicity
Vaccine, 2006Co-Authors: Alexander G Pletnev, David E Swayne, Jim Speicher, Alexander A Rumyantsev, Brian R MurphyAbstract:A live attenuated virus vaccine is being developed to protect against West Nile virus (WN) disease in humans. Previously, it was found that chimeric West Nile/dengue viruses (WN/DEN4 and WN/DEN4Delta30) bearing the membrane precursor and envelope protein genes of WN on a backbone of dengue type 4 virus (DEN4) with or without a deletion of 30 nucleotides (Delta30) in the 3' noncoding region of the DEN4 part of the chimeric genome were attenuated and efficacious in mice and monkeys against WN challenge. Here, we report the generation of a clinical lot of WN/DEN4Delta30 virus and its further Preclinical Evaluation for safety and immunogenicity in mice, geese and monkeys. The vaccine candidate had lost neuroinvasiveness in highly sensitive immunodeficient mice inoculated intraperitoneally and had greatly reduced neurovirulence in suckling mice inoculated intracerebrally (IC). Compared to the wild-type WN parent, the chimeric virus was highly restricted in replication in both murine and human neuroblastoma cells as well as in brains of suckling mice. The WN/DEN4Delta30 virus failed to infect geese, indicating that chimerization of WN with DEN4 completely attenuated WN for this avian host. This observation suggests that the WN/DEN4 chimeric viruses would be restricted in their ability to be transmitted from vaccinees to domestic or wild birds. In monkeys, the WN/DEN4Delta30 vaccine candidate was highly immunogenic despite its low level of replication with undetectable viremia. Furthermore, the WN/DEN4Delta30 vaccine virus was safe and readily induced neutralizing antibodies against WN in monkeys immune to each of the four serotypes of dengue virus. These studies confirm the attenuation of WN/DEN4Delta30 for non-human primates, including dengue-immune monkeys, and demonstrate both a highly restricted replication (>10(8)-fold decrease) in the brain of mice inoculated IC and an absence of infectivity for birds, findings that indicate this vaccine should be safe for both the recipient and the environment.
Prithvi Mruthyunjaya - One of the best experts on this subject based on the ideXlab platform.
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Preclinical Evaluation and intraoperative human retinal imaging with a high resolution microscope integrated spectral domain optical coherence tomography device
Retina-the Journal of Retinal and Vitreous Diseases, 2013Co-Authors: Paul Hahn, Justin Migacz, Rachelle V Oconnell, Robin R Vann, Sharon Fekrat, Prithvi Mruthyunjaya, Eric A Postel, Joseph A Izatt, Cynthia A TothAbstract:PURPOSE: The authors have recently developed a high-resolution microscope-integrated spectral domain optical coherence tomography (MIOCT) device designed to enable OCT acquisition simultaneous with surgical maneuvers. The purpose of this report is to describe translation of this device from Preclinical testing into human intraoperative imaging. METHODS: Before human imaging, surgical conditions were fully simulated for extensive Preclinical MIOCT Evaluation in a custom model eye system. Microscope-integrated spectral domain OCT images were then acquired in normal human volunteers and during vitreoretinal surgery in patients who consented to participate in a prospective institutional review board-approved study. Microscope-integrated spectral domain OCT images were obtained before and at pauses in surgical maneuvers and were compared based on predetermined diagnostic criteria to images obtained with a high-resolution spectral domain research handheld OCT system (HHOCT; Bioptigen, Inc) at the same time point. Cohorts of five consecutive patients were imaged. Successful end points were predefined, including ≥80% correlation in identification of pathology between MIOCT and HHOCT in ≥80% of the patients. RESULTS: Microscope-integrated spectral domain OCT was favorably evaluated by study surgeons and scrub nurses, all of whom responded that they would consider participating in human intraoperative imaging trials. The Preclinical Evaluation identified significant improvements that were made before MIOCT use during human surgery. The MIOCT transition into clinical human research was smooth. Microscope-integrated spectral domain OCT imaging in normal human volunteers demonstrated high resolution comparable to tabletop scanners. In the operating room, after an initial learning curve, surgeons successfully acquired human macular MIOCT images before and after surgical maneuvers. Microscope-integrated spectral domain OCT imaging confirmed preoperative diagnoses, such as full-thickness macular hole and vitreomacular traction, and demonstrated postsurgical changes in retinal morphology. Two cohorts of five patients were imaged. In the second cohort, the predefined end points were exceeded with ≥80% correlation between microscope-mounted OCT and HHOCT imaging in 100% of the patients. CONCLUSION: This report describes high-resolution MIOCT imaging using the prototype device in human eyes during vitreoretinal surgery, with successful achievement of predefined end points for imaging. Further refinements and investigations will be directed toward fully integrating MIOCT with vitreoretinal and other ocular surgery to image surgical maneuvers in real time.
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Preclinical Evaluation and intraoperative human retinal imaging with a high resolution microscope integrated spectral domain optical coherence tomography device
Retina-the Journal of Retinal and Vitreous Diseases, 2013Co-Authors: Paul Hahn, Justin Migacz, Rachelle V Oconnell, Robin R Vann, Sharon Fekrat, Shelley Day, Annie Lee, Phoebe Lin, Anthony N Kuo, Prithvi MruthyunjayaAbstract:Purpose The authors have recently developed a high-resolution microscope-integrated spectral domain optical coherence tomography (MIOCT) device designed to enable OCT acquisition simultaneous with surgical maneuvers. The purpose of this report is to describe translation of this device from Preclinical testing into human intraoperative imaging. Methods Before human imaging, surgical conditions were fully simulated for extensive Preclinical MIOCT Evaluation in a custom model eye system. Microscope-integrated spectral domain OCT images were then acquired in normal human volunteers and during vitreoretinal surgery in patients who consented to participate in a prospective institutional review board-approved study. Microscope-integrated spectral domain OCT images were obtained before and at pauses in surgical maneuvers and were compared based on predetermined diagnostic criteria to images obtained with a high-resolution spectral domain research handheld OCT system (HHOCT; Bioptigen, Inc) at the same time point. Cohorts of five consecutive patients were imaged. Successful end points were predefined, including ≥80% correlation in identification of pathology between MIOCT and HHOCT in ≥80% of the patients. Results Microscope-integrated spectral domain OCT was favorably evaluated by study surgeons and scrub nurses, all of whom responded that they would consider participating in human intraoperative imaging trials. The Preclinical Evaluation identified significant improvements that were made before MIOCT use during human surgery. The MIOCT transition into clinical human research was smooth. Microscope-integrated spectral domain OCT imaging in normal human volunteers demonstrated high resolution comparable to tabletop scanners. In the operating room, after an initial learning curve, surgeons successfully acquired human macular MIOCT images before and after surgical maneuvers. Microscope-integrated spectral domain OCT imaging confirmed preoperative diagnoses, such as full-thickness macular hole and vitreomacular traction, and demonstrated postsurgical changes in retinal morphology. Two cohorts of five patients were imaged. In the second cohort, the predefined end points were exceeded with ≥80% correlation between microscope-mounted OCT and HHOCT imaging in 100% of the patients. Conclusion This report describes high-resolution MIOCT imaging using the prototype device in human eyes during vitreoretinal surgery, with successful achievement of predefined end points for imaging. Further refinements and investigations will be directed toward fully integrating MIOCT with vitreoretinal and other ocular surgery to image surgical maneuvers in real time.
Paul Hahn - One of the best experts on this subject based on the ideXlab platform.
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Preclinical Evaluation and intraoperative human retinal imaging with a high resolution microscope integrated spectral domain optical coherence tomography device
Retina-the Journal of Retinal and Vitreous Diseases, 2013Co-Authors: Paul Hahn, Justin Migacz, Rachelle V Oconnell, Robin R Vann, Sharon Fekrat, Prithvi Mruthyunjaya, Eric A Postel, Joseph A Izatt, Cynthia A TothAbstract:PURPOSE: The authors have recently developed a high-resolution microscope-integrated spectral domain optical coherence tomography (MIOCT) device designed to enable OCT acquisition simultaneous with surgical maneuvers. The purpose of this report is to describe translation of this device from Preclinical testing into human intraoperative imaging. METHODS: Before human imaging, surgical conditions were fully simulated for extensive Preclinical MIOCT Evaluation in a custom model eye system. Microscope-integrated spectral domain OCT images were then acquired in normal human volunteers and during vitreoretinal surgery in patients who consented to participate in a prospective institutional review board-approved study. Microscope-integrated spectral domain OCT images were obtained before and at pauses in surgical maneuvers and were compared based on predetermined diagnostic criteria to images obtained with a high-resolution spectral domain research handheld OCT system (HHOCT; Bioptigen, Inc) at the same time point. Cohorts of five consecutive patients were imaged. Successful end points were predefined, including ≥80% correlation in identification of pathology between MIOCT and HHOCT in ≥80% of the patients. RESULTS: Microscope-integrated spectral domain OCT was favorably evaluated by study surgeons and scrub nurses, all of whom responded that they would consider participating in human intraoperative imaging trials. The Preclinical Evaluation identified significant improvements that were made before MIOCT use during human surgery. The MIOCT transition into clinical human research was smooth. Microscope-integrated spectral domain OCT imaging in normal human volunteers demonstrated high resolution comparable to tabletop scanners. In the operating room, after an initial learning curve, surgeons successfully acquired human macular MIOCT images before and after surgical maneuvers. Microscope-integrated spectral domain OCT imaging confirmed preoperative diagnoses, such as full-thickness macular hole and vitreomacular traction, and demonstrated postsurgical changes in retinal morphology. Two cohorts of five patients were imaged. In the second cohort, the predefined end points were exceeded with ≥80% correlation between microscope-mounted OCT and HHOCT imaging in 100% of the patients. CONCLUSION: This report describes high-resolution MIOCT imaging using the prototype device in human eyes during vitreoretinal surgery, with successful achievement of predefined end points for imaging. Further refinements and investigations will be directed toward fully integrating MIOCT with vitreoretinal and other ocular surgery to image surgical maneuvers in real time.
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Preclinical Evaluation and intraoperative human retinal imaging with a high resolution microscope integrated spectral domain optical coherence tomography device
Retina-the Journal of Retinal and Vitreous Diseases, 2013Co-Authors: Paul Hahn, Justin Migacz, Rachelle V Oconnell, Robin R Vann, Sharon Fekrat, Shelley Day, Annie Lee, Phoebe Lin, Anthony N Kuo, Prithvi MruthyunjayaAbstract:Purpose The authors have recently developed a high-resolution microscope-integrated spectral domain optical coherence tomography (MIOCT) device designed to enable OCT acquisition simultaneous with surgical maneuvers. The purpose of this report is to describe translation of this device from Preclinical testing into human intraoperative imaging. Methods Before human imaging, surgical conditions were fully simulated for extensive Preclinical MIOCT Evaluation in a custom model eye system. Microscope-integrated spectral domain OCT images were then acquired in normal human volunteers and during vitreoretinal surgery in patients who consented to participate in a prospective institutional review board-approved study. Microscope-integrated spectral domain OCT images were obtained before and at pauses in surgical maneuvers and were compared based on predetermined diagnostic criteria to images obtained with a high-resolution spectral domain research handheld OCT system (HHOCT; Bioptigen, Inc) at the same time point. Cohorts of five consecutive patients were imaged. Successful end points were predefined, including ≥80% correlation in identification of pathology between MIOCT and HHOCT in ≥80% of the patients. Results Microscope-integrated spectral domain OCT was favorably evaluated by study surgeons and scrub nurses, all of whom responded that they would consider participating in human intraoperative imaging trials. The Preclinical Evaluation identified significant improvements that were made before MIOCT use during human surgery. The MIOCT transition into clinical human research was smooth. Microscope-integrated spectral domain OCT imaging in normal human volunteers demonstrated high resolution comparable to tabletop scanners. In the operating room, after an initial learning curve, surgeons successfully acquired human macular MIOCT images before and after surgical maneuvers. Microscope-integrated spectral domain OCT imaging confirmed preoperative diagnoses, such as full-thickness macular hole and vitreomacular traction, and demonstrated postsurgical changes in retinal morphology. Two cohorts of five patients were imaged. In the second cohort, the predefined end points were exceeded with ≥80% correlation between microscope-mounted OCT and HHOCT imaging in 100% of the patients. Conclusion This report describes high-resolution MIOCT imaging using the prototype device in human eyes during vitreoretinal surgery, with successful achievement of predefined end points for imaging. Further refinements and investigations will be directed toward fully integrating MIOCT with vitreoretinal and other ocular surgery to image surgical maneuvers in real time.
Alexander A Rumyantsev - One of the best experts on this subject based on the ideXlab platform.
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chimeric west nile dengue virus vaccine candidate Preclinical Evaluation in mice geese and monkeys for safety and immunogenicity
Vaccine, 2006Co-Authors: Alexander G Pletnev, David E Swayne, Jim Speicher, Alexander A Rumyantsev, Brian R MurphyAbstract:Abstract A live attenuated virus vaccine is being developed to protect against West Nile virus (WN) disease in humans. Previously, it was found that chimeric West Nile/dengue viruses (WN/DEN4 and WN/DEN4Δ30) bearing the membrane precursor and envelope protein genes of WN on a backbone of dengue type 4 virus (DEN4) with or without a deletion of 30 nucleotides (Δ30) in the 3′ noncoding region of the DEN4 part of the chimeric genome were attenuated and efficacious in mice and monkeys against WN challenge. Here, we report the generation of a clinical lot of WN/DEN4Δ30 virus and its further Preclinical Evaluation for safety and immunogenicity in mice, geese and monkeys. The vaccine candidate had lost neuroinvasiveness in highly sensitive immunodeficient mice inoculated intraperitoneally and had greatly reduced neurovirulence in suckling mice inoculated intracerebrally (IC). Compared to the wild-type WN parent, the chimeric virus was highly restricted in replication in both murine and human neuroblastoma cells as well as in brains of suckling mice. The WN/DEN4Δ30 virus failed to infect geese, indicating that chimerization of WN with DEN4 completely attenuated WN for this avian host. This observation suggests that the WN/DEN4 chimeric viruses would be restricted in their ability to be transmitted from vaccinees to domestic or wild birds. In monkeys, the WN/DEN4Δ30 vaccine candidate was highly immunogenic despite its low level of replication with undetectable viremia. Furthermore, the WN/DEN4Δ30 vaccine virus was safe and readily induced neutralizing antibodies against WN in monkeys immune to each of the four serotypes of dengue virus. These studies confirm the attenuation of WN/DEN4Δ30 for non-human primates, including dengue-immune monkeys, and demonstrate both a highly restricted replication (>10 8 -fold decrease) in the brain of mice inoculated IC and an absence of infectivity for birds, findings that indicate this vaccine should be safe for both the recipient and the environment.
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chimeric west nile dengue virus vaccine candidate Preclinical Evaluation in mice geese and monkeys for safety and immunogenicity
Vaccine, 2006Co-Authors: Alexander G Pletnev, David E Swayne, Jim Speicher, Alexander A Rumyantsev, Brian R MurphyAbstract:A live attenuated virus vaccine is being developed to protect against West Nile virus (WN) disease in humans. Previously, it was found that chimeric West Nile/dengue viruses (WN/DEN4 and WN/DEN4Delta30) bearing the membrane precursor and envelope protein genes of WN on a backbone of dengue type 4 virus (DEN4) with or without a deletion of 30 nucleotides (Delta30) in the 3' noncoding region of the DEN4 part of the chimeric genome were attenuated and efficacious in mice and monkeys against WN challenge. Here, we report the generation of a clinical lot of WN/DEN4Delta30 virus and its further Preclinical Evaluation for safety and immunogenicity in mice, geese and monkeys. The vaccine candidate had lost neuroinvasiveness in highly sensitive immunodeficient mice inoculated intraperitoneally and had greatly reduced neurovirulence in suckling mice inoculated intracerebrally (IC). Compared to the wild-type WN parent, the chimeric virus was highly restricted in replication in both murine and human neuroblastoma cells as well as in brains of suckling mice. The WN/DEN4Delta30 virus failed to infect geese, indicating that chimerization of WN with DEN4 completely attenuated WN for this avian host. This observation suggests that the WN/DEN4 chimeric viruses would be restricted in their ability to be transmitted from vaccinees to domestic or wild birds. In monkeys, the WN/DEN4Delta30 vaccine candidate was highly immunogenic despite its low level of replication with undetectable viremia. Furthermore, the WN/DEN4Delta30 vaccine virus was safe and readily induced neutralizing antibodies against WN in monkeys immune to each of the four serotypes of dengue virus. These studies confirm the attenuation of WN/DEN4Delta30 for non-human primates, including dengue-immune monkeys, and demonstrate both a highly restricted replication (>10(8)-fold decrease) in the brain of mice inoculated IC and an absence of infectivity for birds, findings that indicate this vaccine should be safe for both the recipient and the environment.
