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Coimmunization with an Optimized IL-15 Plasmid Results in Enhanced Function and Longevity of CD8 T Cells That Are Partially Independent of CD4 T Cell Help
Journal article   Open access   Peer reviewed

Coimmunization with an Optimized IL-15 Plasmid Results in Enhanced Function and Longevity of CD8 T Cells That Are Partially Independent of CD4 T Cell Help

Michele A. Kutzler, Tara M. Robinson, Michael A. Chattergoon, Daniel K. Choo, Andrew Y. Choo, Philip Y. Choe, Mathura P. Ramanathan, Rose Parkinson, Sagar Kudchodkar, Yutaka Tamura, …
The Journal of immunology (1950), v 175(1)
01 Jul 2005
PMID: 15972637
url
https://doi.org/10.4049/jimmunol.175.1.112View
Published, Version of Record (VoR) Open

Abstract

Abstract DNA vaccines are a promising technology for the induction of Ag-specific immune responses, and much recent attention has gone into improving their immune potency. In this study we test the feasibility of delivering a plasmid encoding IL-15 as a DNA vaccine adjuvant for the induction of improved Ag-specific CD8+ T cellular immune responses. Because native IL-15 is poorly expressed, we used PCR-based strategies to develop an optimized construct that expresses 80-fold higher than the native IL-15 construct. Using a DNA vaccination model, we determined that immunization with optimized IL-15 in combination with HIV-1gag DNA constructs resulted in a significant enhancement of Ag-specific CD8+ T cell proliferation and IFN-γ secretion, and strong induction of long-lived CD8+ T cell responses. In an influenza DNA vaccine model, coimmunization with plasmid expressing influenza A PR8/34 hemagglutinin with the optimized IL-15 plasmid generated improved long term CD8+ T cellular immunity and protected the mice against a lethal mucosal challenge with influenza virus. Because we observed that IL-15 appeared to mostly adjuvant CD8+ T cell function, we show that in the partial, but not total, absence of CD4+ T cell help, plasmid-delivered IL-15 could restore CD8 secondary immune responses to an antigenic DNA plasmid, supporting the idea that the effects of IL-15 on CD8+ T cell expansion require the presence of low levels of CD4 T cells. These data suggest a role for enhanced plasmid IL-15 as a candidate adjuvant for vaccine or immunotherapeutic studies.

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Immunology
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