Abstract
BACKGROUND: Due to concern over i) expiration of currently available calf-lymph vaccine (Dryvax); ii) calf lymph as a vaccine (bovine spongiform encephalopathy [BSE], other possible contaminations and animal welfare); and iii) use of variola as a weapon for bioterrorism, a new and safer vaccinia-based smallpox vaccine derived from new cell culture-based technology was proposed. Federally funded work by Acambis, Inc. resulted in FDA approval for ACAM2000 in August 2007. OBJECTIVES: This paper describes the development from conception to FDA approval of the new vaccinia cell cultured-based smallpox vaccine ACAM2000. METHODS: Data were compiled from available public reports. RESULTS/CONCLUSIONS: The studies with ACAM2000 indicate that it closely matches the safety of Dryvax in both non-clinical and clinical trials. ACAM2000 met two of the four primary surrogate efficacy end point criteria established for the Phase III clinical trials. Concern over the incidence of myopericarditis with ACAM2000 and Dryvax exists. So far the cardiac events seem to be self-limited. There are no pediatric safety data for ACAM2000. Overall, clinical trial results were sufficient to convince the FDA that ACAM2000 is a suitable replacement for Dryvax in the event of bioterrorism involving variola (smallpox).