The aim of this application is to develop an improved vaccine for protection against smallpox. This vaccine will be based on attenuating mutations that we have identified in vaccinia virus. These mutations decrease neurovirulence of vaccinia virus 1,000 to >100,000-fold, but still provide excellent protection against challenge with a pathogenic poxvirus. These viruses are also reduced for pathogenesis in immune-compromised mice. Since encephalitis and disseminated disease in immune-compromised humans are amongst the most severe complications to use of vaccinia virus as a vaccine, these mutants should be safer to use than the currently available strains of vaccinia virus. We are proposing to insert these mutations into a strain of vaccinia virus that is appropriate for use in humans (NYCBH), under conditions that will allow use of these viruses in humans. Strains will be analyzed in mice for pathogenesis and for induction of a protective immune response.
| Denzler, Karen L; Babas, Tahar; Rippeon, Amy et al. (2011) Attenuated NYCBH vaccinia virus deleted for the E3L gene confers partial protection against lethal monkeypox virus disease in cynomolgus macaques. Vaccine 29:9684-90 |
| Denzler, Karen L; Schriewer, Jill; Parker, Scott et al. (2011) The attenuated NYCBH vaccinia virus deleted for the immune evasion gene, E3L, completely protects mice against heterologous challenge with ectromelia virus. Vaccine 29:9691-6 |
| Brandt, Teresa; Heck, Michael C; Vijaysri, Sangeetha et al. (2005) The N-terminal domain of the vaccinia virus E3L-protein is required for neurovirulence, but not induction of a protective immune response. Virology 333:263-70 |
