SALMONELLA VACCINES THAT DELIVER BOTH ANTIGEN &CYTOKINE

  • Heffron, Fred, (PI)

    Project: Research project

    Description

    Attenuated strains of Salmonella have been used as carriers of heterologous
    antigens for human and animal vaccination. in mice, S. typhimurium normally
    infects macrophages in the Peyer's patches of the gut and also cells of the
    liver and the spleen. We will compare the immune response of mice orally-
    inoculated with S. typhimurium which expresses one of two model antigens:
    (l) Simian immunodeficiency virus gag protein (SIV gag) and (2) the B
    subunits of Shiga-like toxin type l (SLT-l) and SLT-ll from
    Enterohemorragic E. coli. One of these strains, designed to enhance a
    cellular immune response to an antigen, will deliver DNA encoding the IL-1
    2 cytokine and the SIV gag protein directly to macrophages which will then
    appropriately transcribe, translate, and process these proteins. To do
    this, the Salmonella strain will contain two sets of prokaryotic genes
    under a tightly regulated promoter that after phagocytosis will 1) liberate
    the bacteria from the phagosome into the cytoplasm of a macrophage, and
    then 2) lyse the bacterium thereby releasing a prokaryotic/eukaryotic
    shuttle vector carrying cytokine and viral DNA into the cytoplasm of the
    macrophage. Those macrophages infected with the Salmonella carrier strains
    will process the antigen and co-express specific cytokines thus resulting
    in a targeted and specific enhanced immune response. One of the other
    strains, designed to augment a mucosal immunity, will co-express IL-5, a
    cytokine that augments slgA production, together with the SLT protective
    antigens. finally, we will use the Salmonella vaccine system to evaluate
    the type of T cell response generated to a heterologous antigen that is
    delivered via a vaccine strain directly to the cytoplasm of an antigen
    presenting cell. The results from these studies have direct application to
    the production of effective vaccines that can specifically modulate the
    immune system to develop a protective response against intracellular and
    extracellular pathogens.
    StatusFinished
    Effective start/end date9/30/945/31/06

    Funding

    • National Institutes of Health: $339,750.00
    • National Institutes of Health: $138,279.00
    • National Institutes of Health
    • National Institutes of Health
    • National Institutes of Health: $339,750.00
    • National Institutes of Health: $339,750.00
    • National Institutes of Health: $133,087.00
    • National Institutes of Health: $339,750.00
    • National Institutes of Health: $339,750.00
    • National Institutes of Health

    Fingerprint

    Salmonella Vaccines
    Macrophages
    Salmonella
    gag Gene Products
    Cytokines
    Simian Immunodeficiency Virus
    Cytoplasm
    Antigens
    Epitopes
    Heterophile Antigens
    Vaccines
    HIV
    Shiga Toxins
    Bacteria
    Peyer's Patches
    Phagosomes
    Mucosal Immunity
    Histocompatibility Antigens Class II
    Interleukin-5
    Viral DNA

    ASJC

    • Medicine(all)
    • Immunology and Microbiology(all)