Antiviral cytotoxic T-cell memory by vaccination with recombinant Listeria monocytogenes

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

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    44 Scopus citations

    Abstract

    Listeria monocytogenes is a facultative intracellular bacterium that is able to escape phagocytic vesicles and replicate in the cytoplasm of infected cells. As with viral vectors, this intracytoplasmic life cycle provides a means for introducing foreign proteins into the major histocompatibility complex class I pathway of antigen presentation. Using recombinant L. monocytogenes (rLM) strains expressing the full-length nucleoprotein (NP) or a single cytotoxic T-lymphocyte (CTL) epitope from lymphocytic choriomeningitis virus (LCMV), we analyzed antiviral CTL responses induced by rLM vaccination. After vaccination, rLM was cleared from the host within 7 days while inducing an LCMV-specific ex vivo CD8+ effector CTL response. Virus-specific CTL memory was maintained for 6 months postvaccination, as demonstrated by vigorous secondary CTL responses after in vitro stimulation. A single immunization with rUM that expressed either the full-length NP gene or the CTL epitope alone resulted in LCMV NP-specific CTL precursor frequencies of approximately 1/104 CD8+ T cells. A second rLM vaccination resulted in enhanced virus-specific CTL activity and in vitro proliferation. rLM-vaccinated mice were protected against chronic viral infection by an accelerated virus-specific memory CTL response. These mice cleared infectious virus as well as viral antigen, suggesting that sterilizing immunity was achieved. In contrast to mice that received wild-type LM, rLM-vaccinated mice were protected from vitally induced immunosuppression and splenic atrophy associated with chronic LCMV infection. The ability to elicit long-term cell- mediated immunity is fundamental in designing vaccines against intracellular pathogens, and these results demonstrate the efficacy of recombinant LM vaccination for inducing protective antiviral CTL memory.

    Original languageEnglish (US)
    Pages (from-to)2902-2910
    Number of pages9
    JournalJournal of virology
    Volume70
    Issue number5
    StatePublished - May 3 1996

    ASJC Scopus subject areas

    • Microbiology
    • Immunology
    • Insect Science
    • Virology

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    Slifka, M. K., Shen, H., Matloubian, M., Jensen, E. R., Miller, J. F., & Ahmed, R. (1996). Antiviral cytotoxic T-cell memory by vaccination with recombinant Listeria monocytogenes. Journal of virology, 70(5), 2902-2910.