TY - JOUR
T1 - A computationally designed antigen eliciting broad humoral responses against SARS-CoV-2 and related sarbecoviruses
AU - Vishwanath, Sneha
AU - Carnell, George William
AU - Ferrari, Matteo
AU - Asbach, Benedikt
AU - Billmeier, Martina
AU - George, Charlotte
AU - Sans, Maria Suau
AU - Nadesalingam, Angalee
AU - Huang, Chloe Qingzhou
AU - Paloniemi, Minna
AU - Stewart, Hazel
AU - Chan, Andrew
AU - Wells, David Arthur
AU - Neckermann, Patrick
AU - Peterhoff, David
AU - Einhauser, Sebastian
AU - Cantoni, Diego
AU - Neto, Martin Mayora
AU - Jordan, Ingo
AU - Sandig, Volker
AU - Tonks, Paul
AU - Temperton, Nigel
AU - Frost, Simon
AU - Sohr, Katharina
AU - Ballesteros, Maria Teresa Lluesma
AU - Arbabi, Farzad
AU - Geiger, Johannes
AU - Dohmen, Christian
AU - Plank, Christian
AU - Kinsley, Rebecca
AU - Wagner, Ralf
AU - Heeney, Jonathan Luke
N1 - Publisher Copyright:
© 2023, The Author(s).
PY - 2023
Y1 - 2023
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85172070568&partnerID=8YFLogxK
U2 - 10.1038/s41551-023-01094-2
DO - 10.1038/s41551-023-01094-2
M3 - Article
C2 - 37749309
AN - SCOPUS:85172070568
SN - 2157-846X
JO - Nature Biomedical Engineering
JF - Nature Biomedical Engineering
ER -
