Author: Dalvie, Neil C; Rodriguez-Aponte, Sergio A; Hartwell, Brittany L; Tostanoski, Lisa H; Biedermann, Andrew M; Crowell, Laura E; Kaur, Kawaljit; Kumru, Ozan S; 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; Brunette, Natalie; Wang, Jing Yang; Walkey, Carl; Fiala, Brooke; 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
Title: Engineered SARS-CoV-2 receptor binding domain improves manufacturability in yeast and immunogenicity in mice Cord-id: xbeu3sdt Document date: 2021_1_1
ID: xbeu3sdt
Snippet: Global containment of COVID-19 still requires accessible and affordable vaccines for low- and middle-income countries (LMICs). Recently approved vaccines provide needed interventions, albeit at prices that may limit their global access. Subunit vaccines based on recombinant proteins are suited for large-volume microbial manufacturing to yield billions of doses annually, minimizing their manufacturing cost. These types of vaccines are well-established, proven interventions with multiple safe and
Document: Global containment of COVID-19 still requires accessible and affordable vaccines for low- and middle-income countries (LMICs). Recently approved vaccines provide needed interventions, albeit at prices that may limit their global access. Subunit vaccines based on recombinant proteins are suited for large-volume microbial manufacturing to yield billions of doses annually, minimizing their manufacturing cost. These types of vaccines are well-established, proven interventions with multiple safe and efficacious commercial examples. 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. 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.
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