A computationally designed antigen eliciting broad humoral responses against SARS-CoV-2 and related sarbecoviruses

Vishwanath, Sneha, Carnell, George William, Ferrari, Matteo, Asbach, Benedikt, Billmeier, Martina, George, Charlotte, Sans, Maria Suau, Nadesalingam, Angalee, Huang, Chloe Qingzhou, Paloniemi, Minna, and others. (2023) A computationally designed antigen eliciting broad humoral responses against SARS-CoV-2 and related sarbecoviruses. Nature Biomedical Engineering, . ISSN 2157-846X. (doi:10.1038/s41551-023-01094-2) (KAR id:102968)

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Official URL: https://doi.org/10.1038/s41551-023-01094-2

Abstract

The threat of spillovers of coronaviruses associated with the severe acute respiratory syndrome (SARS) from animals to humans necessitates vaccines that offer broader protection from sarbecoviruses. By leveraging a viral-genome-informed computational method for selecting immune-optimized and structurally engineered antigens, here we show that a single antigen based on the receptor binding domain of the spike protein of sarbecoviruses elicits broad humoral responses against SARS-CoV-1, SARS-CoV-2, WIV16 and RaTG13 in mice, rabbits and guinea pigs. When administered as a DNA immunogen or by a vector based on a modified vaccinia virus Ankara, the optimized antigen induced vaccine protection from the Delta variant of SARS-CoV-2 in mice genetically engineered to express angiotensin-converting enzyme 2 and primed by a viral-vector vaccine (AZD1222) against SARS-CoV-2. A vaccine formulation incorporating mRNA coding for the optimized antigen further validated its broad immunogenicity. Vaccines that elicit broad immune responses across subgroups of coronaviruses may counteract the threat of zoonotic spillovers of betacoronaviruses.

Item Type:	Article
DOI/Identification number:	10.1038/s41551-023-01094-2
Subjects:	Q Science > QR Microbiology > QR355 Virology
Divisions:	Divisions > Division of Natural Sciences > Medway School of Pharmacy
Funders:	Medical Research Council (https://ror.org/03x94j517) Wellcome Trust (https://ror.org/029chgv08)
Depositing User:	Nigel Temperton
Date Deposited:	26 Sep 2023 13:31 UTC
Last Modified:	27 Sep 2023 13:36 UTC
Resource URI:	https://kar.kent.ac.uk/id/eprint/102968 (The current URI for this page, for reference purposes)
Temperton, Nigel J.:	https://orcid.org/0000-0002-7978-3815

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