Abstract
Vaccine strategies aimed at generating CD8(+) T cell memory responses are likely to show augmented efficacy against chronic challenges like tumor. The abundance in variety of memory CD8(+) T cells behooves development of vaccine strategies that generate distinct memory responses and evaluate them for tumor efficacy. In this study, we demonstrate the ability of a variety of rapamycin treatment regimens to regulate virus vaccination-induced CD8(+) T cell memory responses and tumor efficacy. Strikingly, a short course of high-dose, but not low-dose, rapamycin treatment transiently blocks viral vaccination-induced mammalian target of rapamycin activity in CD8(+) T cells favoring persistence and Ag-recall responses over type 1 effector maturation; however, prolonged high-dose rapamycin administration abrogated memory responses. Furthermore, a short course of high-dose rapamycin treatment generated CD8(+) T cell memory responses that were independent of IL-15 and IL-7 and were programmed early for sustenance and greater tumor efficacy. These results demonstrate the impact a regimen of rapamycin treatment has on vaccine-induced CD8(+) T cell responses and indicates that judicious application of rapamycin can augment vaccine efficacy for chronic challenges.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
MeSH terms
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Adjuvants, Immunologic / pharmacology
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Adjuvants, Immunologic / therapeutic use*
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Adoptive Transfer
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Animals
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Antigens, Neoplasm / immunology
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CD8-Positive T-Lymphocytes / drug effects
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CD8-Positive T-Lymphocytes / immunology*
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CD8-Positive T-Lymphocytes / transplantation
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Canarypox virus / immunology
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Cancer Vaccines / administration & dosage
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Cancer Vaccines / therapeutic use*
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Clonal Selection, Antigen-Mediated
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Immunologic Memory / drug effects*
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Interleukin-15 / deficiency
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Interleukin-15 / immunology
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Mechanistic Target of Rapamycin Complex 1
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Mice
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Mice, Inbred C57BL
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Mice, Knockout
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Mice, Transgenic
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Multiprotein Complexes
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Neoplasm Transplantation
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Ovalbumin / administration & dosage
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Ovalbumin / immunology
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Proteins / immunology*
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Sirolimus / pharmacology
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Sirolimus / therapeutic use*
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T-Cell Antigen Receptor Specificity
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TOR Serine-Threonine Kinases
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Thymoma / immunology*
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Thymoma / therapy
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Thymus Neoplasms / immunology*
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Thymus Neoplasms / therapy
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Vaccination*
Substances
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Adjuvants, Immunologic
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Antigens, Neoplasm
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Cancer Vaccines
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Interleukin-15
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Multiprotein Complexes
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Proteins
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Ovalbumin
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Mechanistic Target of Rapamycin Complex 1
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TOR Serine-Threonine Kinases
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Sirolimus