Characterization of CD8+ T cell function and immunodominance generated with an H2O2-inactivated whole-virus vaccie

Joshua M. Walker, Hans Peter Raué, Mark K. Slifka

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    7 Scopus citations

    Abstract

    CD8+ T cells play an important role in protection against both acute and persistent viral infections, and new vaccines that induce CD8+ T cell immunity are currently needed. Here, we show that lymphocytic choriomeningitis virus (LCMV)-specific CD8+ T cells can be generated in response to a nonreplicating H2O2-inactivated whole-virus vaccine (H2O2-LCMV). Vaccineinduced CD8+ T cell responses exhibited an increased ability to produce multiple cytokines at early time points following immunization compared to infection-induced responses. Vaccination with H2O2-LCMV induced the expansion of a narrow subset of the antigen-specific CD8+ T cells induced by LCMV strain Arm infection, resulting in a distinct immunodominance hierarchy. Acute LCMV infection stimulated immunodominance patterns that shifted over time or after secondary infection, whereas vaccine- generated immunodominance profiles remained remarkably stable even following subsequent viral infection. Vaccine-induced CD8+ T cell populations expanded sharply in response to challenge and were then maintained at high levels, with responses to individual epitopes occupying up to 40% of the CD8+ T cell compartment at 35 days after challenge. H2O2-LCMV vaccination protected animals against challenge with chronic LCMV clone 13, and protection was mediated by CD8+ T cells. These results indicate that vaccination with an H2O2-inactivated whole-virus vaccine induces LCMV-specific CD8+ T cells with unique functional characteristics and provides a useful model for studying CD8+ T cells elicited in the absence of active viral infection.

    Original languageEnglish (US)
    Pages (from-to)13735-13744
    Number of pages10
    JournalJournal of virology
    Volume86
    Issue number24
    DOIs
    StatePublished - Dec 1 2012

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    ASJC Scopus subject areas

    • Microbiology
    • Immunology
    • Insect Science
    • Virology

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