E2 Display as a candidate AIDS vaccine

    Project: Research project

    Description

    DESCRIPTION (provided by applicant): New kinds of HIV vaccines are needed to elicit strong immunity, particularly T cell responses. E2DISP, a protein domain from the thermophilic bacterium B. stearothermophilus, self-assembles into 24 nm virus-like particles and can display 60 copies of a foreign antigen on the particle surface. Unlike most other soluble antigens, the E2DISP particle accesses both MHC Class I and Class II pathways, and elicits T cell immunity. T and B cell epitopes of HIV reverse transcriptase made as fusion proteins with E2DISP are effectively presented in vivo and elicited both cytotoxic T cells and antibodies in mice. The overall goal of this proposal is to determine whether whole HIV proteins can be expressed as E2DISP fusion proteins, and whether the resulting particles are immunogenic in mice. We have demonstrated that E2Gag-p17, E2Gag-p24, and E2Gag-p17/24 particles are produced efficiently in this system, and preliminary data suggest that E2Gag-p17 elicits cytotoxic T cells and antibody in mice. We propose to also clone Rev, Tat, Nef, and large regions of Env as E2 fusions, optimize their purification, and assess their antigenicity. Each clone will be used to immunize mice and we will measure CTL activity and antibodies against HIV. We will also assess the possibility of using multiple doses of E2-HIV proteins. Because the E2 complexes can be made in E. coli, and can elicit both cellular and humoral immunity, they have great potential as safe, effective and inexpensive vaccine components.
    StatusFinished
    Effective start/end date3/1/058/28/07

    Funding

    • National Institutes of Health: $229,117.00

    Fingerprint

    AIDS Vaccines
    Human Immunodeficiency Virus Proteins
    T-Lymphocytes
    Immunity
    Clone Cells
    B-Lymphocyte Epitopes
    HIV Reverse Transcriptase
    Antigens
    HIV Antibodies
    T-Lymphocyte Epitopes
    Antibodies
    Humoral Immunity
    Information Systems
    Cellular Immunity
    Virion
    Proteins
    Vaccines
    Escherichia coli
    Bacteria

    ASJC

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