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Modular capsid decoration boosts adenovirus vaccine-induced humoral immunity against SARS-CoV-2.
Dicks, Matthew D J; Rose, Louisa M; Russell, Rebecca A; Bowman, Lesley A H; Graham, Carl; Jimenez-Guardeño, Jose M; Doores, Katie J; Malim, Michael H; Draper, Simon J; Howarth, Mark; Biswas, Sumi.
  • Dicks MDJ; SpyBiotech Ltd, 7600 The Quorum, Oxford Business Park North, Oxford, OX4 2JZ, UK. Electronic address: matthew.dicks@spybiotech.com.
  • Rose LM; SpyBiotech Ltd, 7600 The Quorum, Oxford Business Park North, Oxford, OX4 2JZ, UK.
  • Russell RA; SpyBiotech Ltd, 7600 The Quorum, Oxford Business Park North, Oxford, OX4 2JZ, UK.
  • Bowman LAH; SpyBiotech Ltd, 7600 The Quorum, Oxford Business Park North, Oxford, OX4 2JZ, UK.
  • Graham C; Department of Infectious Diseases, School of Immunology & Microbial Sciences, King's College London, London SE1 9RT, UK.
  • Jimenez-Guardeño JM; Department of Infectious Diseases, School of Immunology & Microbial Sciences, King's College London, London SE1 9RT, UK.
  • Doores KJ; Department of Infectious Diseases, School of Immunology & Microbial Sciences, King's College London, London SE1 9RT, UK.
  • Malim MH; Department of Infectious Diseases, School of Immunology & Microbial Sciences, King's College London, London SE1 9RT, UK.
  • Draper SJ; SpyBiotech Ltd, 7600 The Quorum, Oxford Business Park North, Oxford, OX4 2JZ, UK; Department of Biochemistry, University of Oxford, South Parks Road, Oxford OX1 3QU, UK.
  • Howarth M; SpyBiotech Ltd, 7600 The Quorum, Oxford Business Park North, Oxford, OX4 2JZ, UK; Department of Biochemistry, University of Oxford, South Parks Road, Oxford OX1 3QU, UK.
  • Biswas S; SpyBiotech Ltd, 7600 The Quorum, Oxford Business Park North, Oxford, OX4 2JZ, UK; The Jenner Institute, University of Oxford, Old Road Campus Research Building, Oxford OX3 7DQ, UK.
Mol Ther ; 2022 Aug 10.
Article in English | MEDLINE | ID: covidwho-2257176
ABSTRACT
Adenovirus vector vaccines have been widely and successfully deployed in response to coronavirus disease 2019 (COVID-19). However, despite inducing potent T cell immunity, improvement of vaccine-specific antibody responses upon homologous boosting is modest compared with other technologies. Here, we describe a system enabling modular decoration of adenovirus capsid surfaces with antigens and demonstrate potent induction of humoral immunity against these displayed antigens. Ligand attachment via a covalent bond was achieved using a protein superglue, DogTag/DogCatcher (similar to SpyTag/SpyCatcher), in a rapid and spontaneous reaction requiring only co-incubation of ligand and vector components. DogTag was inserted into surface-exposed loops in the adenovirus hexon protein to allow attachment of DogCatcher-fused ligands on virus particles. Efficient coverage of the capsid surface was achieved using various ligands, with vector infectivity retained in each case. Capsid decoration shielded particles from vector neutralizing antibodies. In prime-boost regimens, adenovirus vectors decorated with the receptor-binding domain of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) spike induced >10-fold higher SARS-CoV-2 neutralization titers compared with an undecorated vector encoding spike. Importantly, decorated vectors achieved equivalent or superior T cell immunogenicity against encoded antigens compared with undecorated vectors. We propose capsid decoration using protein superglues as a novel strategy to improve efficacy and boostability of adenovirus-based vaccines and therapeutics.
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Full text: Available Collection: International databases Database: MEDLINE Topics: Vaccines Language: English Journal subject: Molecular Biology / Therapeutics Year: 2022 Document Type: Article

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Full text: Available Collection: International databases Database: MEDLINE Topics: Vaccines Language: English Journal subject: Molecular Biology / Therapeutics Year: 2022 Document Type: Article