The broad objective of this project is to use conventional and molecular techniques to define the virologicevents following smallpox vaccination in vaccinia-nafve and vaccinia-experienced individuals. The specificalms are to:l )Define the virologic events associated with smallpox vaccination. 2)Determine whether multipleviral variants are present within the Dryvax vaccine, and if so, to investigate their role in the virology ofsmallpox vaccination and in adverse reactions. 3)Define the virologic events associated with adversereactions to smallpox vaccination. 4)Examine the virologic response to treatment with vaccinia immuneglobulin (VIG) and/or cidofovir in vaccinees who require these therapies to control adverse reactions. Aquantitative real-time PCR assay will be developed and used to measure the level of vaccinia DNA at regularintervals after vaccination. Specimens will also be cultured for vaccinia virus. These studies will be useful fordefining the possible contagiousness of individuals having smallpox vacciniation and for helping determinethe need for donor deferral for voluntary blood donations. The data will also provide a basis for studies of theimmunology and immunogentics of vaccinia (Projects 8 and 9). Studies will be performed of Dryvax vaccineto define variants within the vaccine virus. In collaboration with the Genome Sequencing Center, thecomplete nucleotide sequence of 5 variant strains will be determined. Specific assays will be developed andused to define the contribution of variants to immunogenicity and reactogenicity of the vaccine. Smallpoxadverse reaction clinics will be established at each participating medical center to evaluate individuals withpossible adverse reactions. Individuals seen in these clinics will be recruited to participate in detailedstudies of the virology, immunology, and immunogenetics of smallpox vaccination. These studies willinvestigate the virology of adverse reactions, the relationship between viral and immunologic events, and thegenetic basis for both. For individuals having severe adverse reactions, virologic studies will be used to helpevaluate and guide therapy with VIG and cidofovir. The studies described will form a basis for evaluatingDryvax as well as future smallpox vaccines. The assays to be developed and the clinics to be establishedwill provide an infrastructure that will be available to respond to a bioterrorist attack on the United States.
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