Para M.F.,Ohio State University |
Schouten J.,University of Washington |
Rosenkranz S.L.,Harvard University |
Yu S.,Harvard University |
And 9 more authors.
Journal of Acquired Immune Deficiency Syndromes | Year: 2010
BACKGROUND: Mifepristone is a glucocorticoid receptor inhibitor shown in vitro to have anti-HIV activity and anti-simian immunodeficiency virus activity in a macaque model. A phase I/II trial was performed to assess the drug's safety and anti-HIV activity. METHODS: A 28-day double-blind, placebo-controlled trial of mifepristone at doses of 75 mg, 150 mg, and 225 mg given daily was conducted in HIV+ persons with CD4 lymphocyte counts ≥350 cells per cubic millimeter who had no recent antiretroviral therapy. RESULTS: Fifty-six male and 1 female subjects with a median entry CD4 lymphocyte count of 555 cells per cubic millimeter and plasma HIV-1 RNA of 15,623 copies per milliliter were accrued. Forty-five subjects (78.9%) were available for endpoint analysis. In each arm, changes from baseline to day 28 in plasma HIV-1 RNA and CD4 lymphocyte count were not significantly different from zero (no change). There was no relationship between mifepristone trough concentrations and plasma HIV-1 RNA. Day 28 morning plasma cortisol levels were significantly higher in the 150 mg and 225 mg arms compared with placebo, confirming biologic activity, and returned to baseline by day 56. Serum lipids did not change during the trial. Fasting blood sugar was 2.5 mg/dL higher on day 28 in the mifepristone arms, but the Homeostasis Model Assessment of Insulin Resistance (HOMA-IR) did not change. Three subjects (7.3%) receiving mifepristone developed a grade 2 rash. CONCLUSIONS: Mifepristone at doses of 75-225 mg daily was safe and well-tolerated, but did not show significant anti-HIV activity. Copyright © 2010 by Lippincott Williams & Wilkins.
Valentin A.,Center for Cancer Research |
von Gegerfelt A.,Center for Cancer Research |
Rosati M.,Center for Cancer Research |
Miteloudis G.,Center for Cancer Research |
And 8 more authors.
Vaccine | Year: 2010
We have previously reported that therapeutic immunization by intramuscular injection of optimized plasmid DNAs encoding SIV antigens effectively induces immune responses able to reduce viremia in antiretroviral therapy (ART)-treated SIVmac251-infected Indian rhesus macaques. We subjected such therapeutically immunized macaques to a second round of therapeutic vaccination using a combination of plasmids expressing SIV genes and the IL-15/IL-15 receptor alpha as molecular adjuvant, which were delivered by the more efficacious in vivo constant-current electroporation. A very strong induction of antigen-specific responses to Gag, Env, Nef, and Pol, during ART (1.2-1.6% of SIV-specific T cells in the circulating T lymphocytes) was obtained with the improved vaccination method. Immunological responses were characterized by the production of IFN-γ, IL-2, and TNF-α either alone, or in combination as double or triple cytokine positive multifunctional T cells. A significant induction of CD4+ T cell responses, mainly targeting Gag, Nef, and Pol, as well as of CD8+ T cells, mainly targeting Env, was found in both T cells with central memory and effector memory markers. After release from ART, the animals showed a virological benefit with a further ∼1 log reduction in viremia. Vaccination with plasmid DNAs has several advantages over other vaccine modalities, including the possibility for repeated administration, and was shown to induce potent, efficacious, and long-lasting recall immune responses. Therefore, these data support the concept of adding DNA vaccination to the HAART regimen to boost the HIV-specific immune responses.
Khan A.S.,VGX Pharmaceuticals Inc. |
Bodles-Brakhop A.M.,VGX Pharmaceuticals Inc. |
Fiorotto M.L.,Baylor College of Medicine |
Draghia-Akli R.,VGX Pharmaceuticals Inc.
Vaccine | Year: 2010
To differentiate prenatal effects of plasmid growth hormone-releasing hormone (GHRH) treatment from maternal effects mediated by lactation on long-term growth of offspring, a cross-fostering study was designed. Pregnant sows (n = 12) were untreated (n = 6) or received either a Wt-GHRH (n = 2) or HV-GHRH (n = 4) plasmid. At birth, half of each litter was cross-fostered (treated to controls and controls to treated only). Piglets from plasmid-injected sows were heavier at birth (HV-GHRH, 1.65 ± 0.07 kg; Wt-GHRH, 1.46 ± 0.05 kg vs. Controls, 1.27 ± 0.03 kg; P ≥ 0.001) and at weaning (Wt-GHRH, 6.01 ± 0.21 kg and HV-GHRH, 6.34 ± 0.15 kg vs. Controls, 5.37 ± 0.14 kg; P ≥ 0.02, respectively). Control piglets cross-fostered to plasmid-injected sows grew faster to weaning (Wt-GHRH, 5.61 ± 0.15 kg and HV-GHRH, 5.70 ± 0.29 kg vs. Controls, 5.08 ± 0.22 kg; P > 0.05, respectively). Piglets from plasmid-injected sows that suckled on control sows were larger than control piglets on control sows (Wt-GHRH, 5.93 ± 0.20 kg and HV-GHRH, 6.2 ± 0.19 kg vs. Controls, 5.08 ± 0.22 kg; P > 0.05, respectively), but smaller than their littermates left on their treated mothers. The observed improvements were maintained until the end of the study when the offspring were 170-day-old. The results suggest that the improved growth of offspring of GHRH plasmid-treated sows pre-weaning is attributable to improved maternal performance, while after weaning the effects on the pituitary component are relevant. © 2009 Elsevier Ltd. All rights reserved.
Cai Y.,VGX Pharmaceuticals Inc. |
Rodriguez S.,VGXI Inc. |
Rameswaran R.,VGXI Inc. |
Draghia-Akli R.,VGX Pharmaceuticals Inc. |
And 2 more authors.
Vaccine | Year: 2010
The increased use of plasmid-based vaccines to replace their more challenging viral counterparts has increased the demand for high purity and high concentration plasmids. Here we report the production of plasmids encoding different transgenes for DNA vaccine candidates at gram scale with an integrated process consisting of batch fermentation and limited steps of purification. Plasmid products encoding for eight smallpox antigens that were combined into a bioterrorism DNA vaccine exhibited high purity with undetectable RNA, protein and endotoxin, concentration of up to 13.6 mg/mL and supercoiled percentage of 94.5 ± 1.1% after storage at -80 °C for over 1 year. The process has been scaled up for the cGMP manufacture of pharmaceutical-grade human papillomavirus and influenza DNA vaccines up to a 50 g scale, also demonstrating high purity and high concentration. © 2009 Elsevier Ltd. All rights reserved.
Inovio Pharmaceuticals, Inc. and VGX Pharmaceuticals Inc. | Date: 2011-07-26
Pharmaceutical compositions, namely, a nucleotide sequence that encodes an antigen, such as a DNA plasmid having an antigen encoding sequence and like DNA, for the prevention or treatment of acquired immunodeficiency syndrome (AIDS).
VGX Pharmaceuticals LLC | Date: 2011-09-14
An apparatus and a method for isolating a biologic product, such as plasmid DNA, from cells. The method involves lysing cells in a controlled manner separate insoluble components from a fluid lysate containing cellular components of interest, followed by membrane chromatographic techniques to purify the cellular components of interest. The process utilizes a unique lysis apparatus, ion exchange and, optionally, hydrophobic interaction chromatography membranes in cartridge form, and ultrafiltration. The process can be applied to any biologic product extracted from a cellular source. The process uses a lysis apparatus, including a high shear, low residence-time mixer for advantageously mixing a cell suspension with a lysis solution, a hold time that denatures impurities, and an air-sparging bubble mixer that gently yet thoroughly mixes lysed cells with a neutralization/precipiation buffer and floats compacted precipitated cellular material.
Vgx Pharmaceuticals Inc. | Date: 2012-01-25
Aspects of the present invention relate to electroporation devices to effectively facilitate the introduction of a biomolecule into cells of a selected tissue in a body, in particular skin such as intradermic or subcutaneous tissue. In some aspects, the present invention is a skin EP device, which produces a pulse of energy and delivers same to the skin tissue using a skin electrode array and maintains a constant current in the same skin tissue based on user input, including a preset current, and allows the storage and acquisition of current waveform data.
Vgx Pharmaceuticals Llc | Date: 2010-11-17
One aspect of the current invention is an optimized synthetic mammalian expression plasmid with a mutated origin of replication (e.g. mut family of plasmids) comprising a therapeutic element, and a replication element. The therapeutic elements of this plasmid are operatively linked and located in a first operatively-linked arrangement. Additionally, the optimized synthetic mammalian expression plasmid comprises replication elements, wherein the replication elements are operatively linked and located in a second operatively-linked arrangement. The first-operatively-linked arrangement and the second-operatively-linked arrangement comprise a circular structure of the codon optimized synthetic mammalian expression plasmid.
Vgx Pharmaceuticals Llc | Date: 2010-04-16
Devices and methods for delivering an electropermeabilizing pulse of electric energy to a tissue surface to enable delivery into cells in the tissue therapeutic substances. The device incorporates a source capable of generating a sufficient voltage potential to deliver a spark across a gap and delivers same to the tissue surface.
PubMed | VGX Pharmaceuticals Inc.
Type: Journal Article | Journal: Vaccine | Year: 2010
To differentiate prenatal effects of plasmid growth hormone-releasing hormone (GHRH) treatment from maternal effects mediated by lactation on long-term growth of offspring, a cross-fostering study was designed. Pregnant sows (n=12) were untreated (n=6) or received either a Wt-GHRH (n=2) or HV-GHRH (n=4) plasmid. At birth, half of each litter was cross-fostered (treated to controls and controls to treated only). Piglets from plasmid-injected sows were heavier at birth (HV-GHRH, 1.65+/-0.07kg; Wt-GHRH, 1.46+/-0.05kg vs. Controls, 1.27+/-0.03kg; P>or=0.001) and at weaning (Wt-GHRH, 6.01+/-0.21kg and HV-GHRH, 6.34+/-0.15kg vs. Controls, 5.37+/-0.14kg; P>or=0.02, respectively). Control piglets cross-fostered to plasmid-injected sows grew faster to weaning (Wt-GHRH, 5.61+/-0.15kg and HV-GHRH, 5.70+/-0.29kg vs. Controls, 5.08+/-0.22kg; P>0.05, respectively). Piglets from plasmid-injected sows that suckled on control sows were larger than control piglets on control sows (Wt-GHRH, 5.93+/-0.20kg and HV-GHRH, 6.2+/-0.19kg vs. Controls, 5.08+/-0.22kg; P>0.05, respectively), but smaller than their littermates left on their treated mothers. The observed improvements were maintained until the end of the study when the offspring were 170-day-old. The results suggest that the improved growth of offspring of GHRH plasmid-treated sows pre-weaning is attributable to improved maternal performance, while after weaning the effects on the pituitary component are relevant.