Characterization of CD8+ T cell function and immunodominance generated with an H2O2-inactivated whole-virus vaccine.
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 H(2)O(2)-inactivated whole-virus vaccine (H(2)O(2)-LCMV). Vaccine-induced 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 H(2)O(2)-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. H(2)O(2)-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 H(2)O(2)-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.
Oregon National Primate Research Center, Oregon Health & Sciences University, Beaverton, Oregon, USA.
Joshua M
JM
Walker
Hans-Peter
HP
Raué
Mark K
MK
Slifka
D000595:Amino Acid Sequence; D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D016207:Cytokines / Q000096:biosynthesis; D006861:Hydrogen Peroxide / Q000494:pharmacology*; D016056:Immunodominant Epitopes / Q000737:chemistry / Q000276:immunology*; D008217:Lymphocytic choriomeningitis virus / Q000187:drug effects / Q000276:immunology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D016513:Mice, SCID; D008969:Molecular Sequence Data; D014765:Viral Vaccines / Q000276:immunology*
D016207:Cytokines; D016056:Immunodominant Epitopes; D014765:Viral Vaccines; D006861:Hydrogen Peroxide