This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Objective: One of the most feared infectious agents is variola virus, the causative agent of smallpox. Various strains of vaccinia virus (VV) are highly effective in preventing this disease, but can cause complications. Severe illness or death is rare in people with normal immune responses, but considerably more common in individuals with cell-mediated immune defects. The number of individuals that are at risk from this normally innocuous vaccine has greatly increased with the spread of the human immunodeficiency virus (HIV), and it now becomes important to improve the efficacy and safety of this vaccine. Based on our past experience, we propose developing a safer and more efficacious vaccine for smallpox based on the New York City Board of Health (Wyeth) strain of VV that is currently used in the US. We will delete the B8R gene and insertionally inactivate the TK virulence gene with the human IFN-gamma gene to increase attenuation of the virus and the protective cell-mediated immune responses. This recombinant VV will be compared to the parental vaccine in both normal and simian immunodeficiency virus-infected macaques (used as a model for HIV-infected humans) to assess efficacy and safety for normal and immunodeficient individuals.
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