Journal article
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
The Journal of immunology (1950), v 175(1)
01 Jul 2005
PMID: 15972637
Featured in Collection : UN Sustainable Development Goals @ Drexel
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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Details
- Title
- 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
- Creators
- Michele A. Kutzler - University of PennsylvaniaTara M. RobinsonMichael A. Chattergoon - University of PennsylvaniaDaniel K. ChooAndrew Y. Choo - Harvard UniversityPhilip Y. Choe - University of PennsylvaniaMathura P. Ramanathan - University of PennsylvaniaRose Parkinson - University of PennsylvaniaSagar Kudchodkar - University of PennsylvaniaYutaka Tamura - National Institute of Advanced Industrial Science and TechnologyManinder Sidhu - Pearl River Community CollegeVidia Roopchand - Pearl River Community CollegeJ. Joseph KimGeorge N. Pavlakis - National Institutes of HealthBarbara K. Felber - National Institutes of HealthThomas A. Waldmann - National Institutes of HealthJean D. Boyer - University of PennsylvaniaDavid B. Weiner - University of Pennsylvania
- Publication Details
- The Journal of immunology (1950), v 175(1)
- Publisher
- American Association of Immunologists (AAI)
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Infectious Diseases (and HIV Medicine)
- Web of Science ID
- WOS:000230050900015
- Scopus ID
- 2-s2.0-21244447927
- Other Identifier
- 991020550344204721
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- Collaboration types
- Industry collaboration
- Domestic collaboration
- International collaboration
- Web of Science research areas
- Immunology