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

Research output: Contribution to journalArticlepeer-review

8 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 2012

ASJC Scopus subject areas

  • Microbiology
  • Immunology
  • Insect Science
  • Virology

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