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VACCINE RESEARCH

Unique Th1/Th2 Phenotypes Induced during Priming and Memory Phases by Use of Interleukin-12 (IL-12) or IL-28B Vaccine Adjuvants in Rhesus Macaques

Matthew P. Morrow, Jian Yan, Panyupa Pankhong, Bernadette Ferraro, Mark G. Lewis, Amir S. Khan, Niranjan Y. Sardesai, David B. Weiner
Matthew P. Morrow
1Department of Pathology and Laboratory Medicine, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania
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Jian Yan
1Department of Pathology and Laboratory Medicine, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania
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Panyupa Pankhong
1Department of Pathology and Laboratory Medicine, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania
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Bernadette Ferraro
1Department of Pathology and Laboratory Medicine, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania
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Mark G. Lewis
2BioQual, Inc., Rockville, Maryland
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Amir S. Khan
3Inovio Biomedical Corporation, Blue Bell, Pennsylvania
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Niranjan Y. Sardesai
3Inovio Biomedical Corporation, Blue Bell, Pennsylvania
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David B. Weiner
1Department of Pathology and Laboratory Medicine, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania
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  • For correspondence: dbweiner@mail.med.upenn.edu
DOI: 10.1128/CVI.00181-10
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  • FIG. 1.
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    FIG. 1.

    Group design, immunization schedule, and gating strategy. (A) Rhesus macaques were divided into 3 groups that received various immunizations consisting of HIV antigens with or without IL-12 or IL-28B/IFN-λ3 adjuvant. (B) Animals were immunized three times 1 month apart, with an initial immune analysis 2 weeks after the final vaccination. Immune analysis also occurred 3 months after the final vaccination. (C) A representative gating strategy is shown for flow cytometry-based identification of IFN-γ- and IL-4-positive lymphocytes (in this case CD4+ T cells). FSC, forward scatter; SSC, side scatter.

  • FIG. 2.
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    FIG. 2.

    Analysis of the effects of the IL-12 and IL-28B/IFN-λ3 adjuvants on antigen-specific IFN-γ and IL-4 production in T cells. (A) Two weeks after the final vaccination, peripheral CD4+ and CD8+ T cells were assayed for the production of IL-4 and IFN-γ. (B) Total IL-4 and IFN-γ responses are graphed to allow intragroup and intergroup comparison of responses. *, P < 0.05 for intragroup comparison of IL-4 and IFN-γ responses. IFNg, IFN-γ.

  • FIG. 3.
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    FIG. 3.

    Analysis of the effects of IL-12 and IL-28B/IFN-λ3 adjuvants on long-lived responses from T cells. (A) Three months after the final vaccination, peripheral CD4+ and CD8+ T cells were again assayed for the production of IL-4 and IFN-γ. (B) Total IFN-γ production from all T cells (top left) and IL-4 production from all responding T cells (top right) are shown. Relative contributions of IFN-γ and IL-4 to the T cell immune response are shown by group (bottom). *, P < 0.05 for intragroup comparison of IL-4 and IFN-γ responses. IFNg, IFN-γ.

  • FIG. 4.
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    FIG. 4.

    Cumulative overview of the ability of the IL-12 and IL-28B/IFN-λ3 adjuvants to affect the Th1/Th2 axis in the short term and long term. (A) Pie charts show relative contributions of Th1 and Th2 cytokines to the total T cell response, as well as broken down into CD8+ and CD4+ T cell responses, 2 weeks after the final immunization. (B) Pie charts show relative contributions of Th1 and Th2 cytokines to the total T cell response, as well as broken down into CD8+ and CD4+ T cell responses, 3 months after the final immunization. (C) Before-and-after plots show the Th1-skewing capabilities of the adjuvants 2 weeks after the final immunization in comparison with the Th1 levels 3 months after the final immunization in CD8+ T cells, CD4+ T cells, and total T cells. Tables display the hierarchies of Th1-biased responses driven by the adjuvants.

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Unique Th1/Th2 Phenotypes Induced during Priming and Memory Phases by Use of Interleukin-12 (IL-12) or IL-28B Vaccine Adjuvants in Rhesus Macaques
Matthew P. Morrow, Jian Yan, Panyupa Pankhong, Bernadette Ferraro, Mark G. Lewis, Amir S. Khan, Niranjan Y. Sardesai, David B. Weiner
Clinical and Vaccine Immunology Sep 2010, 17 (10) 1493-1499; DOI: 10.1128/CVI.00181-10

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Unique Th1/Th2 Phenotypes Induced during Priming and Memory Phases by Use of Interleukin-12 (IL-12) or IL-28B Vaccine Adjuvants in Rhesus Macaques
Matthew P. Morrow, Jian Yan, Panyupa Pankhong, Bernadette Ferraro, Mark G. Lewis, Amir S. Khan, Niranjan Y. Sardesai, David B. Weiner
Clinical and Vaccine Immunology Sep 2010, 17 (10) 1493-1499; DOI: 10.1128/CVI.00181-10
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    • ABSTRACT
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KEYWORDS

Adjuvants, Immunologic
cytokines
Interleukin-12
Th1 cells
Th2 Cells
vaccines

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