Recombinant Listeria monocytogenes as a live vaccine vehicle for the induction of protective anti-viral cell-mediated immunity

Hao Shen, Mark K. Slifka, Mehrdad Matloubian, Eric R. Jensen, Rafi Ahmed, Jeff F. Miller

    Research output: Contribution to journalArticle

    198 Scopus citations

    Abstract

    Listeria monocytogenes (LM) is a Gram-positive bacterium that is able to enter host cells, escape from the endocytic vesicle, multiply within the cytoplasm, and spread directly from cell to cell without encountering the extracellular milieu. The ability of LM to gain access to the host cell cytosol allows proteins secreted by the bacterium to efficiently enter the pathway for major histocompatibility complex class i antigen processing and presentation. We have established a genetic system for expression and secretion of foreign antigens by recombinant strains, based on stable site- specific integration of expression cassettes into the LM genome. The ability of LM recombinants to induce protective immunity against a heterologous pathogen was demonstrated with lymphocytic choriomeningitis virus (LCMV). LM strains expressing the entire LCMV nucleoprotein or an H-2L(d)-restricted nucleoprotein epitope (an 118-126) were constructed. Immunization of mice with LM vaccine strains conferred protection against challenge with virulent strains of LCMV that otherwise establish chronic infection in naive adult mice. In vivo depletion of CD8+ T cells from vaccinated mice abrogated their ability to clear viral infection, showing that protective anti-viral immunity was due to CD8+ T cells.

    Original languageEnglish (US)
    Pages (from-to)3987-3991
    Number of pages5
    JournalProceedings of the National Academy of Sciences of the United States of America
    Volume92
    Issue number9
    DOIs
    StatePublished - Apr 25 1995

    Keywords

    • CD8 cytotoxic T lymphocytes
    • antigen presentation
    • immunization
    • lymphocytic choriomeningitis virus
    • major histocompatibility complex class I

    ASJC Scopus subject areas

    • General

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