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      A Modular Vaccine Platform Combining Self‐Assembled Peptide Cages and Immunogenic Peptides

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          Abstract

          Subunit vaccines use delivery platforms to present minimal antigenic components for immunization. The benefits of such systems include multivalency, self‐adjuvanting properties, and more specific immune responses. Previously, the design, synthesis, and characterization of self‐assembling peptide cages (SAGEs) have been reported. In these, de novo peptides are combined to make hubs that assemble into nanoparticles when mixed in aqueous solution. Here it is shown that SAGEs are nontoxic particles with potential as accessible synthetic peptide scaffolds for the delivery of immunogenic components. To this end, SAGEs functionalized with the model antigenic peptides tetanus toxoid 632‐651 and ovalbumin 323‐339 drive antigen‐specific responses both in vitro and in vivo, eliciting both CD4 + T cell and B cell responses. Additionally, SAGEs functionalized with the antigenic peptide hemagglutinin 518‐526 from the influenza virus are also able to drive a CD8 + T cell response in vivo. This work demonstrates the potential of SAGEs to act as a modular scaffold for antigen delivery, capable of inducing and boosting specific and tailored immune responses.

          Abstract

          Peptide nanoparticles demonstrate potential as synthetic vaccine delivery platforms when functionalized with immunogenic components. Self‐assembling peptide cages (SAGEs) can be functionalized with model antigenic peptides, and drive antigen‐specific responses both in vitro and in vivo. SAGEs are stable to added immunogenic modifications and, combined with their modularity, offer potential as novel scaffolds for subunit vaccines.

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          Author and article information

          Contributors
          caroline.morris@bristol.ac.uk
          D.N.Woolfson@bristol.ac.uk
          andrew.davidson@bristol.ac.uk
          Journal
          Adv Funct Mater
          Adv Funct Mater
          10.1002/(ISSN)1616-3028
          ADFM
          Advanced Functional Materials
          John Wiley and Sons Inc. (Hoboken )
          1616-301X
          1616-3028
          11 January 2019
          21 February 2019
          : 29
          : 8 ( doiID: 10.1002/adfm.v29.8 )
          : 1807357
          Affiliations
          [ 1 ] BrisSynBio University of Bristol Bristol BS8 1TQ UK
          [ 2 ] School of Chemistry University of Bristol Bristol BS8 1TS UK
          [ 3 ] School of Cellular and Molecular Medicine University of Bristol Bristol BS8 1TD UK
          [ 4 ] School of Biochemistry University of Bristol Bristol BS8 1TD UK
          Author notes
          Author information
          https://orcid.org/0000-0002-4797-0317
          https://orcid.org/0000-0002-1311-6446
          https://orcid.org/0000-0002-0394-3202
          https://orcid.org/0000-0002-1136-4008
          Article
          ADFM201807357
          10.1002/adfm.201807357
          7161841
          32313545
          67123917-61db-45fa-a2ac-51f22e234347
          © 2019 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim

          This article is being made freely available through PubMed Central as part of the COVID-19 public health emergency response. It can be used for unrestricted research re-use and analysis in any form or by any means with acknowledgement of the original source, for the duration of the public health emergency.

          History
          : 18 October 2018
          : 18 December 2018
          Page count
          Figures: 8, Tables: 0, Pages: 12, Words: 8682
          Funding
          Funded by: BBSRC , open-funder-registry 10.13039/501100000268;
          Award ID: BB/L01386X/1
          Funded by: Royal Society Wolfson Research Merit Award
          Award ID: WM140008
          Funded by: BrisSynBio CEM Liberty Blue peptide synthesizer
          Award ID: BB/L01386X/1
          Funded by: EPSRC , open-funder-registry 10.13039/501100000266;
          Award ID: EP/K03927X/1
          Categories
          Full Paper
          Full Papers
          Custom metadata
          2.0
          February 21, 2019
          Converter:WILEY_ML3GV2_TO_JATSPMC version:5.8.0 mode:remove_FC converted:16.04.2020

          coiled coils,peptide design,self‐assembly,subunit vaccines,synthetic biology

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