• Login
    View Item 
    •   UMB Digital Archive
    • School, Graduate
    • Theses and Dissertations All Schools
    • View Item
    •   UMB Digital Archive
    • School, Graduate
    • Theses and Dissertations All Schools
    • View Item
    JavaScript is disabled for your browser. Some features of this site may not work without it.

    Browse

    All of UMB Digital ArchiveCommunitiesPublication DateAuthorsTitlesSubjectsThis CollectionPublication DateAuthorsTitlesSubjects

    My Account

    LoginRegister

    Statistics

    Display statistics

    In vivo characterization of the murine intranasal model for immunologic assessment of Salmonella typhi vaccine and live vector strains and use of this model to assess an S. typhi live vector strain expressing a Plasmodium falciparum antigen

    • CSV
    • RefMan
    • EndNote
    • BibTex
    • RefWorks
    Find Full text
    Author
    Pickett, Thames Emily
    Advisor
    Levine, Myron M. (Myron Max), 1944-
    Date
    1999
    Type
    dissertation
    
    Metadata
    Show full item record
    Abstract
    Attenuated Salmonella typhi live vector vaccine strains are highly immunogenic in mice following intranasal, but not orogastric inoculation. To elucidate the relationship between organs within which vaccine organisms are found and the induction of specific serum IgG antibodies, we examined the in vivo distribution of S. typhi vaccine strain CVD 908-htrA following intranasal administration. Vaccine organisms were cultured from the nasal-associated lymphoid tissue (NALT), lungs, and Peyer's patches two minutes after intranasal inoculation. Vaccine organisms persisted longer in NALT than in other organs. By decreasing the volume of intranasal inoculum containing 109 CFU (from a single 30 mul or 10 mul dose to four 2.5 mul doses given over the course of one hour), we were able to significantly reduce the number of vaccine organisms isolated from the lungs (p < 0.05), without reducing the number of vaccine organisms in NALT. Reducing the number of vaccine organisms in the lungs resulted in a significant decrease in the serum tetanus antitoxin response elicited by CVD 908-htrA expressing tetanus toxin fragment C under the control of the redox-responsive nir15 promoter. In contrast, a similar construct expressing tetanus toxin fragment C under control of the constitutive lpp promoter stimulated a strong serum IgG tetanus antitoxin response with both inoculation regimens. The data suggest that following intranasal inoculation, the NALT is a sufficient inductive site for elicitation of an immune response against both the live vector and heterologous antigen and, as occurs following oral inoculation of humans, attenuated S. typhi vaccine organisms elicit serum IgG responses. The murine intranasal model was used to assess the immunogenicity of CVD 908-htrA expressing an antigen from Plasmodium falciparum, the etiological agent of human malaria. A truncated version of the circumsporozoite protein (tCSP) was expressed as a translational fusion to tetanus toxin fragment C, under the control of either the nir15 or the ompC promoter. Mice inoculated with both constructs mounted appreciable serum IgG responses against S. typhi LPS; serum IgG responses against the fusion protein were weak or non-existent. However mice inoculated with both constructs exhibited specific lymphoproliferative responses against the live vector, tetanus toxoid and CSP.
    Description
    University of Maryland, Baltimore. Ph.D. 1999
    Keyword
    Biology, Molecular
    Biology, Microbiology
    Health Sciences, Immunology
    Administration, Intranasal
    Plasmodium falciparum--immunology
    Salmonella typhi
    Vaccines, Attenuated
    Identifier to cite or link to this item
    http://hdl.handle.net/10713/1305
    Collections
    Theses and Dissertations All Schools
    Theses and Dissertations School of Medicine

    entitlement

     
    DSpace software (copyright © 2002 - 2023)  DuraSpace
    Quick Guide | Policies | Contact Us | UMB Health Sciences & Human Services Library
    Open Repository is a service operated by 
    Atmire NV
     

    Export search results

    The export option will allow you to export the current search results of the entered query to a file. Different formats are available for download. To export the items, click on the button corresponding with the preferred download format.

    By default, clicking on the export buttons will result in a download of the allowed maximum amount of items.

    To select a subset of the search results, click "Selective Export" button and make a selection of the items you want to export. The amount of items that can be exported at once is similarly restricted as the full export.

    After making a selection, click one of the export format buttons. The amount of items that will be exported is indicated in the bubble next to export format.