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    Vaccinia recombinants as probes of relevant HSV-2-specific immunity

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    Author
    Wachsman, Matthew
    Advisor
    Aurelian, Laure
    Date
    1991
    Type
    dissertation
    
    Metadata
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    Abstract
    Vaccinia recombinants expressing the glycoprotein D (gD) of HSV-1 (VP176) or HSV-2 (VP221) under control of an early vaccinia virus promoter or of HSV-1 under the control of a late promoter (VP254) were studied as probes for relevant immunity. The recombinants expressed comparable amounts of gD and grew equally well in vitro and in vivo VP176 immunization protected guinea pigs against primary (p {dollar}<{dollar} 0.005) and recurrent (p {dollar}<{dollar} 0.005) cutaneous HSV-2 disease, VP221 protected against recurrent disease and VP254 immunization afforded no protection. All vaccines protected mice at 10 days post infection, but VP176 gave superior protection on day 50 post immunization (p {dollar}<{dollar} 0.0001). Although neutralizing anti-HSV antibody and immunity to vaccinia antigens induced were identical, immunization with VP176 as compared to VP254 induced significantly higher levels of T-cell mediated immunity to HSV antigen as defined by lymphocyte transformation or delayed type hypersensitivity (P {dollar}<{dollar} 0.01). L3T4+ LNC from VP176 immunized animals mediated these effects and could transfer protection but required a second non-HSV immune, radiosensitive cell. Immunity induced by prior HSV-2 immunization was less effective than that induced by VP176 in terms of preventing primary disease (p {dollar}<{dollar} 0.01) and local viral replication (100 fold higher virus titers). This was associated with lower HSV-specific blastogenic and DTH response in HSV but not VP176 immune animals following HSV reexposure. VP254 but not VP176 infected antigen presenting cells failed to produce fully glycosylated gD. This defect correlated with the failure of VP254 infected epidermal or spleen cells to express gD on the cell surface or to present antigen.
    Description
    University of Maryland, Baltimore. Pharmacology & Experimental Therapeutics. Ph.D. 1991
    Keyword
    Biology, Microbiology
    Health Sciences, Pharmacology
    Health Sciences, Immunology
    vaccinia recombinants
    Herpesvirus 2, Human--immunology
    Vaccinia virus
    Identifier to cite or link to this item
    http://hdl.handle.net/10713/2566
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    Theses and Dissertations All Schools
    Theses and Dissertations School of Medicine

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