Scientific Publications by FDA Staff

Biologicals 2010 Mar;38(2):278-83

A mouse-based assay for the pre-clinical neurovirulence assessment of vaccinia virus-based smallpox vaccines.

Zhang CX, Sauder C, Malik T, Rubin SA

Post-vaccinal encephalitis, although relatively uncommon, is a known adverse event associated with many live, attenuated smallpox vaccines. Although smallpox vaccination ceased globally in 1980, vaccine manufacture has resumed in response to concerns over the possible use of smallpox virus as an agent of bioterrorism. To better support the production of safer smallpox vaccines, we previously reported the development of a mouse model in which a relatively attenuated vaccine strain (Dryvax((R))) could be discerned from a more virulent laboratory strain (WR). Here we have further tested the performance of this assay by evaluating the neurovirulence of several vaccinia virus-based smallpox vaccines spanning a known range in neurovirulence for humans. Our data indicate that testing of 10-100pfu of virus in mice following intracranial inoculation reliably assesses the virus's neurovirulence potential for humans.