Journal
VIROLOGY
Volume 331, Issue 1, Pages 151-158Publisher
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.virol.2004.10.022
Keywords
herpes simplex virus; TLR9 ligand; IL-12; IL-15; anti-CD40 mAb; memory CD8(+) T cells
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Funding
- NIAID NIH HHS [R01 AI 4646 201] Funding Source: Medline
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The capability of cellular immune components to rapidly recall upon challenge in most situations decides the efficacy of a vaccine. Here, we show that immunization of mice with SSIEFARL peptide (immunodominant epitope in glycoprotein B of herpes simplex virus type 1, aa498-505) combined with TLR9 ligand in the absence of helper CD4(+) T cell activation generates a functionally impaired CDS- T cell memory response. Codelivery of IL-12 IL-15, or anti-CD40 together with MHC class-I-restricted peptide combined with TLR9 ligand at inception of immunization resulted in generation of memory CD8(+) T cells that were several fold less; compromised than immunization with peptide alone. Furthermore, administration of either plasmid DNA encoding IL-15 or anti-CD40 mAb but not rIL-12 during the memory, phase restored the reactivity of memory CD8(+) T cells. Moreover, the rescued CD8(+) T cells preserved their cytotoxic capability and were able to clear a recombinant vaccinia virus encoding glycoprotein B of HSV. Our results indicate that good memory CD8(-) T cell response to peptide immunization can be achieved by using costimulatory procedures at the time of priming or recall immunization. (C) 2004 Elsevier Inc. All rights reserved.
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