Over the recent years, plasmid DNA vaccines have reached licensure against infectious hematopoietic necrosis virus in farmed salmon (Canada), West Nile virus in horses and metastatic melanoma in dogs (United States). A number of approaches are currently evaluated in clinical trials to enhance the potency of DNA vaccines in humans, including formulation of DNA with delivery systems and adjuvants as well as administration of DNA with devices. This presentation will report on the development of TransVaxTM, a poloxamer-formulated therapeutic DNA vaccine against human cytomegalovirus (CMV) in transplant patients. A vaccine that increases CMV-specific T-cell responses could reduce CMV reactivation after transplantation, thus decreasing the use of antiviral drugs and preventing CMV-associated disease. The interim analysis of a randomized, placebo-controlled Phase 2 trial in hematopoietic stem cell transplant (HCT) recipients will be presented. In a multicenter trial conducted in the United States, CMV-seropositive recipients undergoing allogeneic, matched HCT received either TransVaxTM (n=40) or placebo (n=34) at 3-5 days prior to and 3-6, 12 and 28 weeks after transplant. Viral load, antiviral use and immunogenicity endpoints will be discussed. In addition, the development of prophylactic DNA vaccine candidates against H5N1 and H1N1 pandemic influenza using the adjuvant Vaxfectin® will be described. In particular, the safety and immunogenicity of a Vaxfectin®-formulated DNA vaccine encoding the influenza virus H5 hemagglutinin in clinical trials will be reported. Two double-blind, placebo-controlled Phase 1 trials were conducted in approximately 100 healthy 18-45 year old adults at three sites in the United States using intramuscular injections with either needle or needle-free Biojector® 2000 device. Levels and kinetics of hemagglutination inhibition (HI) titers, neutralizing antibody titers and cross-clade HI titers will be reported. Interferon-ã-producing H5-specific T-cell responses will also be described.
Alain Rolland, "CLINICAL DEVELOPMENT OF FORMULATED THERAPEUTIC AND PROPHYLACTIC DNA-BASED VACCINES" in "Vaccine Technology III", Eds, ECI Symposium Series, Volume P13 (2010). http://dc.engconfintl.org/vaccine_iii/7