Vishwanath, Sneha and Carnell, George William and Ferrari, Matteo and Asbach, Benedikt and Billmeier, Martina and George, Charlotte and Sans, Maria Suau and Nadesalingam, Angalee and Huang, Chloe Qingzhou and Paloniemi, Minna and Stewart, Hazel and Chan, Andrew and Wells, David Arthur and Neckermann, Patrick and Peterhoff, David and Einhauser, Sebastian and Cantoni, Diego and Neto, Martin Mayora and Jordan, Ingo and Sandig, Volker and Tonks, Paul and Temperton, Nigel and Frost, Simon and Sohr, Katharina and Ballesteros, Maria Teresa Lluesma and Arbabi, Farzad and Geiger, Johannes and Dohmen, Christian and Plank, Christian and Kinsley, Rebecca and Wagner, Ralf and Heeney, Jonathan Luke (2023) A computationally designed antigen eliciting broad humoral responses against SARS-CoV-2 and related sarbecoviruses. NATURE BIOMEDICAL ENGINEERING. ISSN 2157-846X
Full text not available from this repository. (Request a copy)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. A computationally designed antigen based on the receptor binding domain of the spike protein of sarbecoviruses elicits broad humoral responses against severe acute respiratory syndrome viruses in mice, rabbits and guinea pigs.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | LENTIVIRAL VECTOR; MESSENGER-RNA; GENE DELIVERY; PROTEIN; TRANSDUCTION; EXPRESSION; PREDICTION; ANTIBODY; CELLS; RBD |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Medizinische Mikrobiologie und Hygiene |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 20 Mar 2024 06:05 |
| Last Modified: | 20 Mar 2024 06:05 |
| URI: | https://pred.uni-regensburg.de/id/eprint/60061 |
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