A mouse-based assay for the pre-clinical neurovirulence assessment of vaccinia virus-based smallpox vaccines.
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) 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 10-100 pfu of virus in mice following intracranial inoculation reliably assesses the virus's neurovirulence potential for humans.
Zhang
Cheryl X
CX
FDA, Division of Viral Products, Lincoln Drive, Bethesda, MD 20892, USA.
Sauder
Christian
C
Malik
Tahir
T
Rubin
Steven A
SA
D000818:Animals; D000831:Animals, Newborn; D001921:Brain / Q000473:pathology / Q000821:virology; D002478:Cells, Cultured; D002642:Chick Embryo; D002522:Chlorocebus aethiops; D004353:Drug Evaluation, Preclinical; D004673:Encephalomyelitis, Acute Disseminated / Q000175:diagnosis* / Q000209:etiology / Q000401:mortality / Q000473:pathology; D051379:Mice; D023421:Models, Animal; D012900:Smallpox Vaccine / Q000009:adverse effects* / Q000627:therapeutic use*; D013997:Time Factors; D014615:Vaccinia / Q000150:complications / Q000401:mortality / Q000473:pathology / Q000821:virology; D014616:Vaccinia virus / Q000276:immunology*; D014709:Vero Cells; D014774:Virulence; D014779:Virus Replication / Q000502:physiology
D012900:Smallpox Vaccine