GEN-003-Presented Work

Presentations

IDWeek 2017, San Diego, California, October 4-8, 2017


42nd Annual International Herpesvirus Workshop, Ghent, Belgium, July 29 - August 2, 2017


IDWeek 2016, New Orleans, Louisiana, October 26-30, 2016


41st Annual International Herpesvirus Workshop, Madison, Wisconsin, July 23-27, 2016


American Society of Microbiology’s ASM Microbe 2016, Boston, June 19, 2016


Infectious Disease Society of America’s IDWeek 2015TM, San Diego, October 9, 2015


40th Annual International Herpesvirus Workshop, Boise, Idaho, July 25-29, 2015


25th European Congress of Clinical Microbiology and Infectious Diseases (ECCMID) Copenhagen, Denmark, April 25-29, 2015


Infectious Disease Society of America’s IDWeek 2014TM, Philadelphia, October 11, 2014


39th Annual International Herpesvirus Workshop, Kobe, Japan July 19-23, 2014


World Vaccine Congress 24-26 March, 2014


Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC) Denver CO, September 10-13, 2013

 

Publications

Therapeutic Vaccine for Genital Herpes Simplex Virus-2 Infection: Findings from a Randomized Trial

David I Bernstein et al. doi:10.1093/infdis/jix004

GEN-003, a novel therapeutic vaccine for HSV-2 currently in clinical development was shown to have an acceptable safety profile, reduce viral shedding, reduce the frequency of genital lesions and boost the humoral and cellular immune responses to HSV-2.


Immune responses elicited by the GEN-003 candidate HSV-2 therapeutic vaccine in a randomized controlled dose-ranging phase 1/2a trial

Jessica Baker Flechtner et al. doi:10.1016/j.vaccine.2016.09.001

This article describes the T cell and antibody responses that were elicited in subjects who participated in the GEN-003-001 clinical trial.


Development of a high-throughput β-Gal-based neutralization assay for quantitation of herpes simplex virus-neutralizing antibodies in human samples

Amy Baccari et al. doi:10.1016/j.vaccine.2016.05.033

The NIAID held a workshop in 2012 to discuss the challenges that face the development of herpes simplex vaccines. One recommendation was harmonization and standardization of assays, including the HSV antibody neutralization assay.  Conventional plaque reduction assays can be very subjective and therefore not reproducible between laboratories. To answer that call, this paper describes the development of a colorimetric HSV neutralization assay that is less subjective than plaque assays, is more high throughput, and importantly, results in concordant data across different laboratories and with disparate HSV colorimetric neutralizing antibody assays.


Evolution of rational vaccine designs for genital herpes immunotherapy

Johanna K. Kaufmann, Jessica. B. Flechtner. Current Opinion in Virology 17 (2016) 80-86

In this article, we review vaccine approaches for genital herpes that currently show pre-clinical and clinical promise. Technologic improvements in antigen discovery and growing understanding of immune responses to HSV-2 have driven the evolution of design of effective immunotherapies. Here, we outline the conceptual progress in vaccine development, the current state of immunotherapies, and novel approaches that may improve the efficacy of next generation vaccines.


Summary and recommendations from a National Institute of Allergy and Infectious Diseases (NIAID) workshop on “Next Generation Herpes Simplex Virus Vaccines”

 David M. Knipe et al.  Vaccine 32 (2014) 1561-1562


Identification of novel virus-specific antigens by CD4+ and CD8+ T cells from asymptomatic HSV-2 seropositive and seronegative donors

 Long, D et al. (2014) Virology 464-465: 296-311.

The white blood components called T cells have been identified as a critical contributors to human immunity against HSV-2 disease and reactivation. This article describes the use of ATLAS™ to identify protein targets of T cell responses that are associated with natural protection in human subjects exposed to or infected with HSV-2. First, the ATLAS™ library generation and validation is described, followed by a comparison of the similarities and differences in CD4+ and CD8+ T cell responses between individuals who are infected and fail to control their disease, who are infected but do not have symptomatic outbreaks, or who are exposed through an infected partner but do not become infected. The results provide evidence that antibodies are insufficient for natural control of disease and that T cell responses to a subset of protein targets (antigens) are over-represented in people who naturally control their disease. In addition, there are some preliminary data that suggest the specificity, and not necessarily the breadth of response, is a key to prevention of infection.

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An adjuvanted herpes simplex virus 2 subunit vaccine elicits a T cell response in mice and is an effective therapeutic vaccine in Guinea pigs

Skoberne, M et al. (2013) J Virol 87(7): 3930-42

This paper summarizes the preclinical characterization of the immunotherapeutic vaccine, GEN-003, for which a phase 1/2a clinical trial has been initiated. This is the first publication showing that antigens identified through ATLAS screening of an HSV-2 proteomic library using T cells from HSV-2-infected or -exposed human subjects protect guinea pigs against herpes reactivation when administered as a therapeutic vaccine. The article goes on to demonstrate that in addition to dramatic reduction of symptomatic disease, there is a statistically significant reduction in the frequency of viral shedding in immunized animals.