PHASE 2 TRIAL FOR VENEZUELAN EQUINE ENCEPHALITIS V3526 -
DESCRIPTION (provided by applicant): DVC is responsible for the advanced development and ultimate licensure of vaccines designed to protect against a range of biological agents. One vaccine is a new live-attenuated virus vaccine, V3526, demonstrated to protect against the effects of infection with Venezuelan Equine Encephalitis (VEE) virus. The viruses causing VEE are antigenically related, mosquito-borne viruses that are members of the Togavirus family, genus Alphavirus. Although outbreaks occur only occasionally, these viruses can spread rapidly through large populations. DVC proposes that once a VEE vaccine becomes widely available, the value of VEE as a biological weapon will be significantly reduced. There are six subtypes of VEE virus (I-VI), with subtype I comprising several varieties (A-F). The subtypes responsible for large equine epizootics are IA/B, and IC. However, enzootic strains of VEE such as IE and IIIA are also known to be highly virulent for man and would constitute equally effective biological warfare agents. V3526 vaccination provides protection against aerosol challenge (multiple subtypes) in murine, equine, and non-human primate models. The V3526 candidate vaccine did not induce any measurable viremia or observable clinical symptoms such as significant fever, diarrhea, inactivity, or anorexia in either equines or non-human primates. The overall objective of the proposed project is the fast-track development of a safe and efficacious vaccine against VEE that will provide maximal immunologic protection against subtypes IA/B, IC, IE, and IIIA. DVC is currently manufacturing a clinical lot of V3526 vaccine for a phase 1 trial to initiate in 2004, funded by the Department of Defense. The manufacturing, lot release and toxicology strategy has been reviewed by the FDA. Two nonclinical lots have been produced and tested extensively in animals. The specific aims of the proposed project are to optimize the production process, including scale-up and lyophilization of V3526 vaccine, to manufacture a clinical lot of V3526 for a phase 2 trial, and to complete a phase 2 clinical trial.
