Exploiting a high dose murine challenge model for HSV to identify potential DNA prime subunit boost vaccine strategies that could be translated to human clinical trials
10th Euro Global Summit and Expo on Vaccines & Vaccination
June 16-18, 2016 Rome, Italy

Timothy R Fouts

Profectus Biosciences Inc., USA

Scientific Tracks Abstracts: J Vaccines Vaccin

Abstract:

HSV-2 causes a serious disease for which an effective vaccine has not been developed. A recombinant glycoprotein D (gD) vaccine (HerpeVac) recently failed to show efficacy in a phase III trial despite showing promise in animal studies. When we modify the murine challenge model to employ significantly higher challenge dose, we could achieve level of protection with a HerpeVac like vaccine consisting of recombinant soluble gD protein formulated in an AS04 like adjuvant (e.g., alum+MPL) that was quite similar to that observed in human clinical trials. We exploited this new, more predictive, model to evaluate DNA immunization strategies using HSV-2 gD expressing DNA vaccine. The hypothesis tested was that an IL-12 adjuvanted DNA vaccine expressing HSV-2 gD would be significantly more protective than a gD used alone. Mice were immunized on days 0 and 21 with gD and IL-12 expressing plasmids by electroporation with a HerpeVac like vaccine or with a potent live attenuated HSV-2 0�?NLS vaccine that had demonstrated a high degree of protection in this modified model. All mice were vaginally challenged on day 81 with 2,000 times the LD50 of HSV-2 MS. Virus shedding; survival and weight loss/regain were monitored for 30 days post challenge and compared using Mann-Whitney Rank Sum Tests. Survival was compared using Log Rank tests. The gD DNA vaccine statistically reduced virus shedding, weight loss and death compared to the HerpeVac like vaccine. The survival and weight loss profiles of DNA immunized mice were more similar to those of HSV-2 0�?NLS vaccinated mice than to HerpeVac like vaccinated mice. Binding antibody titers to gD did not correlate with protection, whereas neutralizing titers and IgG1/IgG2A ratios did correlate. CD4+ but not CD8+ cells were also found to play a substantial role in protection. Thus, the gD immunogen delivered as a DNA vaccine was significantly more protective than the same immunogen delivered as a recombinant protein formulated in an AS04 like adjuvant.

Biography :

Timothy R Fouts is the Co-Founders and Principle Scientists at Profectus Biosciences, USA. He directs a team of scientists in the discovery and preclinical development of vaccines, small molecule and antibody based antiviral therapies and microbicides that are within the Profectus research portfolio, in particular HIV and certain biothreat viruses. He has more than 35 scientific publications that appeared in peer reviewed journals and book chapters. He has received his PhD in Immunology from the University of Maryland, Baltimore and completed Postdoctoral Fellowship at the Aaron Diamond AIDS Research Center at Rockefeller University in NYC.

Email: fouts@profectusbiosciences.com