A computationally designed antigen eliciting broad humoral responses against SARS-CoV-2 and related sarbecoviruses
Sneha Vishwanath, George Carnell, Matteo Ferrari, Benedikt Asbach, Martina Billmeier, Charlotte George, Maria Suau Sans, Angalee Nadesalingam, Chloe Qingzhou Huang, Minna Paloniemi, Hazel Stewart, Andrew Chan, David A. Wells, Patrick Neckermann, David Peterhoff, Sebastian Einhauser, Diego Cantoni, Martin Mayora Neto, Ingo Jordan, Volker Sandig, Paul Tonks, Nigel Temperton, Simon D. W. Frost, Katharina Sohr, Maria Teresa Lluesma Ballesteros, Farzad Arbabi, Johannes Geiger, Christian Dohmen, Christian Plank, Rebecca Kinsley, Ralf Wagner, Jonathan L. Heeney
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.