Engineered SARS-CoV-2 receptor binding domain improves immunogenicity in mice and elicits protective immunity in hamsters

Dalvie, Neil C.; Rodriguez-Aponte, Sergio A.; Hartwell, Brittany L.; Tostanoski, Lisa H.; Biedermann, Andrew M.; Crowell, Laura E.; Kaur, Kawaljit; Kumru, Ozan; Carter, Lauren; Yu, Jingyou; Chang, Aiquan; McMahan, Katherine; Courant, Thomas; Lebas, Celia; Lemnios, Ashley A.; Rodrigues, Kristen A.; Silva, Murillo; Johnston, Ryan S.; Naranjo, Christopher A.; Tracey, Mary Kate; Brady, Joseph R.; Whittaker, Charles A.; Yun, Dongsoo; Kar, Swagata; Porto, Maciel; Lok, Megan; Andersen, Hanne; Lewis, Mark G.; Love, Kerry R.; Camp, Danielle L.; Silverman, Judith Maxwell; Kleanthous, Harry; Joshi, Sangeeta B.; Volkin, David B.; Dubois, Patrice M.; Collin, Nicolas; King, Neil P.; Barouch, Dan H.; Irvine, Darrell J.; Love, J. Christopher

Global containment of COVID-19 still requires accessible and affordable vaccines for low- and middle-income countries (LMICs).(1) Recently approved vaccines provide needed interventions, albeit at prices that may limit their global access.(2) Subunit vaccines based on recombinant proteins are suited for large-volume microbial manufacturing to yield billions of doses annually, minimizing their manufacturing costs.(3) These types of vaccines are well-established, proven interventions with multiple safe and efficacious commercial examples.(4–6) Many vaccine candidates of this type for SARS-CoV-2 rely on sequences containing the receptor-binding domain (RBD), which mediates viral entry to cells via ACE2.(7,8) Here we report an engineered sequence variant of RBD that exhibits high-yield manufacturability, high-affinity binding to ACE2, and enhanced immunogenicity after a single dose in mice compared to the Wuhan-Hu-1 variant used in current vaccines. Antibodies raised against the engineered protein exhibited heterotypic binding to the RBD from two recently reported SARS-CoV-2 variants of concern (501Y.V1/V2). Presentation of the engineered RBD on a designed virus-like particle (VLP) also reduced weight loss in hamsters upon viral challenge.