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Bioengineered small extracellular vesicles deliver multiple SARS-CoV-2 antigenic fragments and drive a broad immunological response.

Published version
Peer-reviewed

Repository DOI


Change log

Authors

Long, Heather M 
Yam-Puc, Juan Carlos 
Haigh, Tracey A 

Abstract

The COVID-19 pandemic highlighted the clear risk that zoonotic viruses pose to global health and economies. The scientific community responded by developing several efficacious vaccines which were expedited by the global need for vaccines. The emergence of SARS-CoV-2 breakthrough infections highlights the need for additional vaccine modalities to provide stronger, long-lived protective immunity. Here we report the design and preclinical testing of small extracellular vesicles (sEVs) as a multi-subunit vaccine. Cell lines were engineered to produce sEVs containing either the SARS-CoV-2 Spike receptor-binding domain, or an antigenic region from SARS-CoV-2 Nucleocapsid, or both in combination, and we tested their ability to evoke immune responses in vitro and in vivo. B cells incubated with bioengineered sEVs were potent activators of antigen-specific T cell clones. Mice immunised with sEVs containing both sRBD and Nucleocapsid antigens generated sRBD-specific IgGs, nucleocapsid-specific IgGs, which neutralised SARS-CoV-2 infection. sEV-based vaccines allow multiple antigens to be delivered simultaneously resulting in potent, broad immunity, and provide a quick, cheap, and reliable method to test vaccine candidates.

Description

Publication status: Published


Funder: NIHR Cambridge Biomedical Research Centre; doi: http://dx.doi.org/10.13039/501100018956

Keywords

SARS-CoV-2, antigen, extracellular vesicles, immune presentation, vaccine, Animals, Humans, Mice, SARS-CoV-2, Pandemics, COVID-19, Extracellular Vesicles, Vaccines

Journal Title

J Extracell Vesicles

Conference Name

Journal ISSN

2001-3078
2001-3078

Volume Title

13

Publisher

Wiley
Sponsorship
Wellcome Trust (216370/Z/19/Z)
Wellcome Trust (204845/Z/16/Z)
MRC (via University of Birmingham) (MR/V028448/1)
MRC (MR/T032413/1)