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Molecular engineering and plant expression of an immunoglobulin heavy chain scaffold for delivery of a dengue vaccine candidate.

Abstract

In order to enhance vaccine uptake by the immune cells in vivo, molecular engineering approach was employed to construct a Polymeric Immunoglobulin G Scaffold (PIGS) that incorporates multiple copies of an antigen and targets the Fc gamma receptors on antigen-presenting cells. These self-adjuvanting immunogens were tested in the context of dengue infection, for which there is currently no globally licensed vaccine yet. Thus, the consensus domain III sequence (cEDIII) of dengue glycoprotein E was incorporated into PIGS and expressed in both tobacco plants and Chinese Ovary Hamster cells. Purified mouse and human cEDIII-PIGS were fractionated by HPLC into low and high molecular weight forms, corresponding to monomers, dimers and polymers. cEDIII-PIGS were shown to retain important Fc receptor functions associated with immunoglobulins, including binding to C1q component of the complement and the low affinity Fcγ receptor II, as well as to macrophage cells in vitro. These molecules were shown to be immunogenic in mice, with or without an adjuvant, inducing a high level IgG antibody response which showed a neutralising potential against the dengue virus serotype 2. The cEDIII-PIGS also induced a significant cellular immune response, IFN-γ production and polyfunctional T-cells in both the CD4+ and CD8+ compartments. This proof-of-principle study shows that the potent antibody Fc-mediated cellular functions can be harnessed to improve vaccine design, underscoring the potential of this technology to induce and modulate a broad-ranging immune response. This article is protected by copyright. All rights reserved.

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  • Authors+Show Affiliations

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    Institute for Infection and Immunity, St George's University of London, UK. Department of Molecular Biology and The Institute for Molecular Biology and Genetics, Chonbuk National University, Jeonju, 54896, Korea.

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    Institute for Infection and Immunity, St George's University of London, UK.

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    Institute for Infection and Immunity, St George's University of London, UK.

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    Institute for Infection and Immunity, St George's University of London, UK.

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    Institute for Infection and Immunity, St George's University of London, UK.

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    Institute for Infection and Immunity, St George's University of London, UK.

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    School of Life Sciences, Arizona State University, Tempe, AZ, USA.

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    School of Life Sciences, Arizona State University, Tempe, AZ, USA.

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    School of Life Sciences, Arizona State University, Tempe, AZ, USA.

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    Department of Molecular Biology and The Institute for Molecular Biology and Genetics, Chonbuk National University, Jeonju, 54896, Korea.

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    Department of Molecular Biology and The Institute for Molecular Biology and Genetics, Chonbuk National University, Jeonju, 54896, Korea.

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    Institute for Infection and Immunity, St George's University of London, UK.

    Institute for Infection and Immunity, St George's University of London, UK.

    Source

    Plant biotechnology journal : 2017 Apr 19 pg

    Pub Type(s)

    Journal Article

    Language

    eng

    PubMed ID

    28421694