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Targeting antigen to the surface of EVs improves the in vivo immunogenicity of human and non-human adenoviral vaccines in mice

Bliss, Carly M., Parsons, Andrea J., Nachbagauer, Raffael, Hamilton, Jennifer R., Cappuccini, Federica, Ulaszewska, Marta, Webber, Jason P., Clayton, Aled, Hill, Adrian V.S. and Coughlan, Lynda 2020. Targeting antigen to the surface of EVs improves the in vivo immunogenicity of human and non-human adenoviral vaccines in mice. Molecular Therapy - Methods and Clinical Development 16 , pp. 108-125. 10.1016/j.omtm.2019.12.003

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Abstract

Adenoviral (Ad) vectors represent promising vaccine platforms for infectious disease. To overcome pre-existing immunity to commonly used human adenovirus serotype 5 (Ad5), vectors based on rare species or non-human Ads are being developed. However, these vectors often exhibit reduced potency compared with Ad5, necessitating the use of innovative approaches to augment the immunogenicity of the encoded antigen (Ag). To achieve this, we engineered model Ag, enhanced green fluorescent protein (EGFP), for targeting to the surface of host-derived extracellular vesicles (EVs), namely exosomes. Exosomes are nano-sized EVs that play important roles in cell-to-cell communication and in regulating immune responses. Directed targeting of Ag to the surface of EVs/exosomes is achieved by “exosome display,” through fusion of Ag to the C1C2 domain of lactadherin, a protein highly enriched in exosomes. Herein, we engineered chimpanzee adenovirus ChAdOx1 and Ad5-based vaccines encoding EGFP, or EGFP targeted to EVs (EGFP_C1C2), and compared vaccine immunogenicity in mice. We determined that exosome display substantially increases Ag-specific humoral immunity following intramuscular and intranasal vaccination, improving the immunological potency of both ChAdOx1 and Ad5. We propose that this Ag-engineering approach could increase the immunogenicity of diverse Ad vectors that exhibit desirable manufacturing characteristics, but currently lack the potency of Ad5.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Medicine
Publisher: Elsevier
ISSN: 2329-0501
Funders: HC Roscoe Grant 2016 from the British Medical Association Foundation for Medical Research
Date of First Compliant Deposit: 31 January 2020
Date of Acceptance: 12 December 2019
Last Modified: 31 Mar 2020 14:52
URI: http://orca-mwe.cf.ac.uk/id/eprint/129212

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