Donald Fine’s research while affiliated with Computer Sciences Corp and other places

DynPort Vaccine Company (DVC) LLC, a CSC Company, is under a contract with the United States Department of Defense Joint Vaccine Acquisition Program (JVAP) to develop, test and license safe and efficacious vaccines against biowarfare agents. As part of this program DVC is conducting a comprehensive toxicological assessment of the safety of V3526, a live attenuated Venezuelan Equine Encephalitis (VEE) vaccine candidate. Our review of the published pre-clinical toxicology literature, together with the data collected from DVC-sponsored investigations indicated V3526 was comparatively safer and more efficacious than TC-83, the current VEE Investigational New Drug (IND) status vaccine. Non-clinical toxicity studies on experimental systems ranging from mouse, guinea pig, equine and non-human primates (NHP) consistently revealed the V3526 vaccine candidate superior in terms of safety and related toxicological parameters such as neurovirulence when compared with the TC-83. Our experimental investigations indicated that V3526 may conform to the key requirements of a VEE virus vaccine, in that, (a) it elicits a high level of immunogenic response in mice and hamsters, both sensitive to VEE-induced pathologies, and (b) it induces a protective response in the NHP model when challenged with either virulent IA/B or IE viruses. Additional studies are underway to further confirm these findings.

A hazard assessment of Venezuelan equine encephalitis (VEE) virus sub-types and vaccine candidates was performed according to standard risk assessment procedures. Data from published literature demonstrates a considerable degree of safety of V3526 when compared to TC-83 vaccine, the protective measure that has been used to protect laboratory workers for over four decades. V3526 is a new recombinant vaccine candidate that is a vastly different product with a diminished hazard to public health and the general environment. A weight-of-evidence (WOE)-based scheme was employed to assign weights for relevance, quality, and adequacy of evidence in published literature on medical pathology, epidemiology, pre-clinical investigational studies, and environmental studies. The results of this assessment indicated that V3526 has a low adverse impact on public health and the general environment. Although there are currently no human infectivity or pathogenicity data for V3526, existing evidence from published experimental animal studies reveals a diminished hazard for environmental transmission and distribution. Recently, the US Centers for Disease Control and Prevention (CDC) excluded V3526 from select agent requirements set forth under the Health and Human Services (HHS) regulations in Title 42 C.F.R. Part 73 and the US Department Agriculture (USDA) regulations set forth in Title 7 C.F.R. Part 331 and Title 9 C.F.R. Part 121. This paper summarizes the background, rationale, and hazard analysis used for assessing the environmental hazard of the VEE vaccine candidate strain V3526.