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

Jackson, Hannah K.; Long, Heather M.; Yam‐Puc, Juan Carlos; Palmulli, Roberta; Haigh, Tracey A.; Gerber, Pehuén Pereyra; Lee, Jin S.; Matheson, Nicholas J.; Young, Lesley; Trowsdale, John; Lo, Mathew; Taylor, Graham S.; Thaventhiran, James E.; Edgar, James R.

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.

Citation

Jackson, H. K., Long, H. M., Yam‐Puc, J. C., Palmulli, R., Haigh, T. A., Gerber, P. P., Lee, J. S., Matheson, N. J., Young, L., Trowsdale, J., Lo, M., Taylor, G. S., Thaventhiran, J. E., & Edgar, J. R. (2024). Bioengineered small extracellular vesicles deliver multiple SARS-CoV-2 antigenic fragments and drive a broad immunological response. Journal of Extracellular Vesicles, 13(2), Article e12412. https://doi.org/10.1002/jev2.12412

• Journal Article Type: Article
• Acceptance Date: Jan 10, 2024
• Online Publication Date: Feb 9, 2024
• Publication Date: 2024-02
• Deposit Date: May 28, 2024
• Publicly Available Date: May 28, 2024
• Journal: Journal of Extracellular Vesicles
• Electronic ISSN: 2001-3078
• Publisher: Taylor & Francis Open Access
• Peer Reviewed: Peer Reviewed
• Volume: 13
• Issue: 2
• Article Number: e12412
• DOI: https://doi.org/10.1002/jev2.12412
• Keywords: antigen; extracellular vesicles; immune presentation; SARS-CoV-2; vaccine
• Public URL: https://nottingham-repository.worktribe.com/output/35430699
• Publisher URL: https://isevjournals.onlinelibrary.wiley.com/doi/10.1002/jev2.12412