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

Kim, M-Y; Van Dolleweerd, C; Copland, A; Paul, MJ; Hofmann, S; Webster, GR; Julik, E; Ceballos-Olvera, I; Reyes-Del Valle, J; Yang, M-S; et al. Kim, M-Y; Van Dolleweerd, C; Copland, A; Paul, MJ; Hofmann, S; Webster, GR; Julik, E; Ceballos-Olvera, I; Reyes-Del Valle, J; Yang, M-S; Jang, Y-S; Reljic, R; Ma, JK (2017) Molecular engineering and plant expression of an immunoglobulin heavy chain scaffold for delivery of a dengue vaccine candidate. Plant Biotechnol J, 15 (12). pp. 1590-1601. ISSN 1467-7652 https://doi.org/10.1111/pbi.12741
SGUL Authors: Paul, Mathew John Copland, Alastair Hofmann, Sven

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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 neutralizing 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.

Item Type: Article
Additional Information: © 2017 The Authors. Plant Biotechnology Journal published by Society for Experimental Biology and The Association of Applied Biologists and John Wiley & Sons Ltd. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
Keywords: dengue, immunoglobulin G, infection, plant biotechnology, vaccine, Immunoglobulin G, dengue, infection, plant biotechnology, vaccine, Biotechnology, 10 Technology, 06 Biological Sciences, 11 Medical And Health Sciences
SGUL Research Institute / Research Centre: Academic Structure > Infection and Immunity Research Institute (INII)
Journal or Publication Title: Plant Biotechnol J
ISSN: 1467-7652
Language: eng
Dates:
DateEvent
21 November 2017Published
15 July 2017Published Online
19 April 2017Published Online
3 April 2017Accepted
Publisher License: Publisher's own licence
Projects:
Project IDFunderFunder ID
2013R1A6A3A03022769National Research Foundation of Koreahttp://dx.doi.org/10.13039/501100003725
NRF - 2014K1B1A1073861National Research Foundation of Koreahttp://dx.doi.org/10.13039/501100003725
PubMed ID: 28421694
Go to PubMed abstract
URI: http://openaccess.sgul.ac.uk/id/eprint/108850
Publisher's version: https://doi.org/10.1111/pbi.12741

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