The Experts below are selected from a list of 24330 Experts worldwide ranked by ideXlab platform
David I Bernstein - One of the best experts on this subject based on the ideXlab platform.
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intranasal nanoemulsion adjuvanted hsv 2 subunit Vaccine is effective as a prophylactic and Therapeutic Vaccine using the guinea pig model of genital herpes
Vaccine, 2019Co-Authors: David I Bernstein, Rhonda D Cardin, Fernando J Bravo, Tarek Hamouda, Derek A Pullum, Gary H Cohen, Vira Bitko, Ali Ibrahim FattomAbstract:Genital herpes is a sexually transmitted disease representing a major global health concern. Currently, there is no approved Vaccine and existing antiviral therapies exhibit limited efficacy. Herein, we describe an intranasal (IN) Vaccine comprised of HSV-2 surface glycoproteins gD2 and gB2 formulated in a nanoemulsion adjuvant (NE01-gD2/gB2). Using the HSV-2 genital herpes guinea pig model, we demonstrate that IN NE01-gD2/gB2 induces higher levels of neutralizing antibody compared to a monovalent IN NE01-gD2 Vaccine, but less than an intramuscular (IM) Alum/MPL-gD2 Vaccine. Following intravaginal (IVag) challenge with HSV-2, the group immunized with IN NE01-gD2/gB2 exhibited significantly reduced acute and recurrent disease scores compared to placebo recipients. Significantly, latent virus was only detected in the dorsal root ganglia of 1 of 12 IN NE01-gD2/gB2-vaccinated animals compared to 11 of 12 placebo recipient. In the Therapeutic model, IN NE01-gD2/gB2 immunized guinea pigs exhibited a significant reduction in the recurrent lesions scores (64%, p < 0.01), number of animal days with disease (64%, p < 0.01), number of animals with viral shedding (50%, p < 0.04) and reduction in virus positive vaginal swabs (56%, p < 0.04), These data suggests that the treatment may be effective in treating chronic disease and minimizing virus transmission. These results warrant advancing the development of IN NE01-gD2/gB2 as both a prophylactic and Therapeutic Vaccine against HSV-2.
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effects of different doses of gen 003 a Therapeutic Vaccine for genital herpes simplex virus 2 on viral shedding and lesions results of a randomized placebo controlled trial
The Journal of Infectious Diseases, 2018Co-Authors: Nicholas Van Wagoner, Kenneth H. Fife, Peter A. Leone, Terri Warren, Richard H Beigi, Lori Panther, Richard M Novak, David I Bernstein, John D. Kriesel, Stephen K. TyringAbstract:Background: GEN-003 is a candidate Therapeutic Vaccine for genital herpes simplex virus type 2 (HSV-2). We compared virologic and clinical impact of varying GEN-003 doses. Methods: Adults with symptomatic HSV-2 received placebo or GEN-003 (30 or 60 µg antigen with 25, 50, or 75 µg adjuvant). Viral shedding and lesion rates before vaccination were compared with those measured immediately after vaccination, then at weeks 29-33 and 53-57 after last dose. Results: Compared with baseline shedding rates, the rate ratios for viral shedding immediately after treatment were as follows: 0.82 (95% confidence interval [CI], 0.49-1.36), 30 µg antigen/25 µg adjuvant (30/25) dose; 0.64 (95% CI, 0.45-0.92), 30/50 dose; 0.63 (95% CI, 0.37-1.10), 30/75 dose; 0.56 (95% CI, 0.36-0.88), 60/25 dose; 0.58 (95% CI, 0.38-0.89), 60/50 dose; 0.45 (95% CI, 0.16-0.79), 60/75 dose; and 0.98 (95% CI, 0.76-1.26), placebo. Lesion rate reductions by GEN-003 ranged from 31% to 69%, but lesion rates also decreased among placebo recipients (62%). Reductions in shedding and lesion rate were durable for 12 months for the 60 µg antigen plus 50 or 75 µg adjuvant groups. No serious adverse events occurred with vaccination. Conclusions: The most efficacious Vaccine combinations for GEN-003 were the 60 µg/50 µg and 60 µg/75 µg doses.
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Therapeutic Vaccine for genital herpes simplex virus 2 infection findings from a randomized trial
The Journal of Infectious Diseases, 2017Co-Authors: David I Bernstein, Kenneth H. Fife, Terri Warren, Stephen K. Tyring, Anna Wald, Patricia Lee, Nicholas Van Wagoner, Amalia Magaret, Jessica Flechtner, Sybil A TaskerAbstract:Background Genital herpes simplex virus type 2 (HSV-2) infection causes recurrent lesions and frequent viral shedding. GEN-003 is a candidate Therapeutic Vaccine containing HSV-2 gD2∆TMR and ICP4.2, and Matrix-M2 adjuvant. Methods Persons with genital herpes were randomized into 3 dose cohorts to receive 3 intramuscular doses 21 days apart of 10 µg, 30 µg, or 100 µg of GEN-003, antigens without adjuvant, or placebo. Participants obtained genital swab specimens twice daily for HSV-2 detection and monitored genital lesions for 28-day periods at baseline and at intervals after the last dose. Results One hundred and thirty-four persons received all 3 doses. Reactogenicity was associated with adjuvant but not with antigen dose or dose number. No serious adverse events were attributed to GEN-003. Compared with baseline, genital HSV-2 shedding rates immediately after dosing were reduced with GEN-003 (from 13.4% to 6.4% for 30 μg [P < .001] and from 15.0% to 10.3% for 100 µg [P < .001]). Lesion rates were also significantly (P < .01) reduced immediately following immunization with 30 µg or 100 µg of GEN-003. GEN-003 elicited increases in antigen binding, virus neutralizing antibody, and T-cell responses. Conclusions GEN-003 had an acceptable safety profile and stimulated humoral and cellular immune responses. GEN-003 at doses of 30 µg and 100 µg reduced genital HSV shedding and lesion rates. Clinical Trials Registration NCT01667341 (funded by Genocea).
Stephen K. Tyring - One of the best experts on this subject based on the ideXlab platform.
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effects of different doses of gen 003 a Therapeutic Vaccine for genital herpes simplex virus 2 on viral shedding and lesions results of a randomized placebo controlled trial
The Journal of Infectious Diseases, 2018Co-Authors: Nicholas Van Wagoner, Kenneth H. Fife, Peter A. Leone, Terri Warren, Richard H Beigi, Lori Panther, Richard M Novak, David I Bernstein, John D. Kriesel, Stephen K. TyringAbstract:Background: GEN-003 is a candidate Therapeutic Vaccine for genital herpes simplex virus type 2 (HSV-2). We compared virologic and clinical impact of varying GEN-003 doses. Methods: Adults with symptomatic HSV-2 received placebo or GEN-003 (30 or 60 µg antigen with 25, 50, or 75 µg adjuvant). Viral shedding and lesion rates before vaccination were compared with those measured immediately after vaccination, then at weeks 29-33 and 53-57 after last dose. Results: Compared with baseline shedding rates, the rate ratios for viral shedding immediately after treatment were as follows: 0.82 (95% confidence interval [CI], 0.49-1.36), 30 µg antigen/25 µg adjuvant (30/25) dose; 0.64 (95% CI, 0.45-0.92), 30/50 dose; 0.63 (95% CI, 0.37-1.10), 30/75 dose; 0.56 (95% CI, 0.36-0.88), 60/25 dose; 0.58 (95% CI, 0.38-0.89), 60/50 dose; 0.45 (95% CI, 0.16-0.79), 60/75 dose; and 0.98 (95% CI, 0.76-1.26), placebo. Lesion rate reductions by GEN-003 ranged from 31% to 69%, but lesion rates also decreased among placebo recipients (62%). Reductions in shedding and lesion rate were durable for 12 months for the 60 µg antigen plus 50 or 75 µg adjuvant groups. No serious adverse events occurred with vaccination. Conclusions: The most efficacious Vaccine combinations for GEN-003 were the 60 µg/50 µg and 60 µg/75 µg doses.
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Therapeutic Vaccine for genital herpes simplex virus 2 infection findings from a randomized trial
The Journal of Infectious Diseases, 2017Co-Authors: David I Bernstein, Kenneth H. Fife, Terri Warren, Stephen K. Tyring, Anna Wald, Patricia Lee, Nicholas Van Wagoner, Amalia Magaret, Jessica Flechtner, Sybil A TaskerAbstract:Background Genital herpes simplex virus type 2 (HSV-2) infection causes recurrent lesions and frequent viral shedding. GEN-003 is a candidate Therapeutic Vaccine containing HSV-2 gD2∆TMR and ICP4.2, and Matrix-M2 adjuvant. Methods Persons with genital herpes were randomized into 3 dose cohorts to receive 3 intramuscular doses 21 days apart of 10 µg, 30 µg, or 100 µg of GEN-003, antigens without adjuvant, or placebo. Participants obtained genital swab specimens twice daily for HSV-2 detection and monitored genital lesions for 28-day periods at baseline and at intervals after the last dose. Results One hundred and thirty-four persons received all 3 doses. Reactogenicity was associated with adjuvant but not with antigen dose or dose number. No serious adverse events were attributed to GEN-003. Compared with baseline, genital HSV-2 shedding rates immediately after dosing were reduced with GEN-003 (from 13.4% to 6.4% for 30 μg [P < .001] and from 15.0% to 10.3% for 100 µg [P < .001]). Lesion rates were also significantly (P < .01) reduced immediately following immunization with 30 µg or 100 µg of GEN-003. GEN-003 elicited increases in antigen binding, virus neutralizing antibody, and T-cell responses. Conclusions GEN-003 had an acceptable safety profile and stimulated humoral and cellular immune responses. GEN-003 at doses of 30 µg and 100 µg reduced genital HSV shedding and lesion rates. Clinical Trials Registration NCT01667341 (funded by Genocea).
Olivier Bouchaud - One of the best experts on this subject based on the ideXlab platform.
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viral rebound in semen after antiretroviral treatment interruption in an hiv Therapeutic Vaccine double blind trial
AIDS, 2019Co-Authors: Romain Palich, Jade Ghosn, Antoine Chaillon, Valerie Boilet, Marielaure Nere, Marielaure Chaix, Pierre Delobel, Jeanmichel Molina, Frederic Lucht, Olivier BouchaudAbstract:Objectives:This study aimed to determine the timing and level of HIV rebound in blood and seminal plasma and to characterize the HIV rebounding populations after antiretroviral treatment interruption (ATI) in HIV-1-infected participants enrolled in a Therapeutic Vaccine trial.Design:A 12-week (W) AT
Patrick C Mcatee - One of the best experts on this subject based on the ideXlab platform.
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characterization and stability of trypanosoma cruzi 24 c4 tc24 c4 a candidate antigen for a Therapeutic Vaccine against chagas disease
Journal of Pharmaceutical Sciences, 2017Co-Authors: Amadeo B Biter, Sarah Weltje, Elissa M Hudspeth, Christopher A Seid, Patrick C McateeAbstract:Abstract Chagas disease due to chronic infection with Trypanosoma cruzi is a neglected cause of heart disease, affecting approximately 6-10 million individuals in Latin America and elsewhere. T. cruzi Tc24, a calcium-binding protein in the flagellar pocket of the parasite, is a candidate antigen for an injectable Therapeutic Vaccine as an alternative or a complement to chemotherapy. Previously, we reported that a genetically engineered construct from which all cysteine residues had been eliminated (Tc24-C4) yields a recombinant protein with reduced aggregation and improved analytical purity in comparison to the wild-type form, without compromising antigenicity and immunogenicity. We now report that the established process for producing Escherichia coli –expressed Tc24-C4 protein is robust and reproducibly yields protein lots with consistent analytical characteristics, freeze-thaw, accelerated, and long-term stability profiles. The data indicate that, like most proteins, Tc24-C4 should be stable at −80°C, but also at 4°C and room temperature for at least 30 days, and up to 7-15 days at 37°C. Thus, the production process for recombinant Tc24-C4 is suitable for Current Good Manufacturing Practice production and clinical testing, based on process robustness, analytical characteristics, and stability profile.
S H Zhou - One of the best experts on this subject based on the ideXlab platform.
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antigen antibody complex as Therapeutic Vaccine for viral hepatitis b
International Reviews of Immunology, 1999Co-Authors: Y M Wen, S H ZhouAbstract:In a previous study, hepatitis B surface antigen (HBsAg) complexed to human anti-HBs immunoglobulins (HBIG) in excess of HBsAg was used as Therapeutic Vaccine to treat chronic hepatitis B patients and promising results were obtained. To study the mechanisms of this approach, mice were immunized with HBsAg or IC (immunogenic complex, i.e. HBsAg complexed with mouse polyclonal anti-HBs). Studies indicate that IC induced enhanced immune responses by increasing uptake of HBsAg through Fc receptors on antigen presenting cells and modulated HBsAg processing and presentation. This modulation led to stimulation of T cell responses, and increased production of IL-2 and IFN-γ. Assay for antibody subclasses showed that higher ratio of IgG 2a was observed in the IC immunized group, which correlated with the production of lymphokine pattern. When alum was used as the adjuvant, though antibody response was enhanced, production of cytokines decreased. When DNA from a recombinant plasmid was added to IC as an adjuvant, t...
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Antigen-antibody complex as Therapeutic Vaccine for viral hepatitis B.
International reviews of immunology, 1999Co-Authors: Y M Wen, S H ZhouAbstract:In a previous study, hepatitis B surface antigen (HBsAg) complexed to human anti-HBs immunoglobulins (HBIG) in excess of HBsAg was used as Therapeutic Vaccine to treat chronic hepatitis B patients and promising results were obtained. To study the mechanisms of this approach, mice were immunized with HBsAg or IC (immunogenic complex, i.e. HBsAg complexed with mouse polyclonal anti-HBs). Studies indicate that IC induced enhanced immune responses by increasing uptake of HBsAg through Fc receptors on antigen presenting cells and modulated HBsAg processing and presentation. This modulation led to stimulation of T cell responses, and increased production of IL-2 and IFN-gamma. Assay for antibody subclasses showed that higher ratio of IgG 2a was observed in the IC immunized group, which correlated with the production of lymphokine pattern. When alum was used as the adjuvant, though antibody response was enhanced, production of cytokines decreased. When DNA from a recombinant plasmid was added to IC as an adjuvant, the titer of anti-HBs was significantly higher than those in mice immunized only with the DNA or the IC. Since DNA immunization can induce both cellular and humoral immune responses, combined immunization using IC and DNA might serve as another type of Therapeutic Vaccine for viral hepatitis B.
