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HIV-1 Env vaccine comprised of electroporated DNA and protein co-administered with Talabostat
Authors:Cristillo Anthony D  Galmin Lindsey  Restrepo Susana  Hudacik Lauren  Suschak John  Lewis Brad  Draghia-Akli Ruxandra  Aziz Nazneen  Weiss Deborah  Markham Phillip  Pal Ranajit
Institution:a Advanced BioScience Laboratories, Inc., 5510 Nicholson Lane, Kensington, MD 20895, USA
b VGX Pharmaceuticals, Inc., Immune Therapeutics Division, 2700 Research Forest Drive, The Woodlands, TX 77381, USA
c Point Therapeutics, 155 Federal Street, Boston, MA 02110, USA
Abstract:Selection of potent yet low reactogenic adjuvants for protein immunization is important for HIV-1 vaccine development. Immunogenicity of electroporated DNA (HIV env) and recombinant gp120, administered with either QS-21 or the orally administered immunomodulator, Talabostat, was evaluated in BALB/c mice. Electroporation of low dose DNA elicited Th1 cytokines and anti-envelope antibodies. Immunization with gp120 protein alone with or without Talabostat elicited lower Th1 and Th2 cytokine levels but comparable anti-gp120 antibodies to QS-21-formulated protein. Boosting of DNA-primed mice with gp120/Talabostat induced similar anti-gp120 antibody titers and slightly higher levels of Th1 and Th2 cytokines relative to QS-21-formulated protein. Induction of CD8+ and CD4+ T cells and functional CTL activity was noted. These results highlight the potential use of orally administered Talabostat for efficient protein boosting of antibody and T-cell responses primed by DNA.
Keywords:HIV-1  Vaccine  Electroporation  Cellular immunity  Humoral immunity  Talabostat
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