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

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

Publication date: Sep 25, 2023

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.

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Concepts Keywords
Betacoronaviruses Antigen
Biomed Broad
Broader Coronaviruses
Rabbits Cov
Vaccinia Humoral
Immune
Optimized
Protection
Sarbecoviruses
Sars
Spillovers
Threat
Vaccine
Vaccines
Viral

Semantics

Type Source Name
disease MESH severe acute respiratory syndrome
disease VO vaccine
drug DRUGBANK Angiotensin II
disease MESH zoonotic spillovers

Original Article

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