Engineered SARS-CoV-2 receptor binding domain improves manufacturability in yeast and immunogenicity in mice.
Neil C Dalvie, Sergio A Rodriguez-Aponte, Brittany L Hartwell, Lisa H Tostanoski, Andrew M Biedermann, Laura E Crowell, Kawaljit Kaur, Ozan S Kumru, Lauren Carter, Jingyou Yu, Aiquan Chang, Katherine McMahan, Thomas Courant, Celia Lebas, Ashley A Lemnios, Kristen A Rodrigues, Murillo Silva, Ryan S Johnston, Christopher A Naranjo, Mary Kate Tracey, Joseph R Brady, Charles A Whittaker, Dongsoo Yun, Natalie Brunette, Jing Yang Wang, Carl Walkey, Brooke Fiala, Swagata Kar, Maciel Porto, Megan Lok, Hanne Andersen, Mark G Lewis, Kerry R Love, Danielle L Camp, Judith Maxwell Silverman, Harry Kleanthous, Sangeeta B Joshi, David B Volkin, Patrice M Dubois, Nicolas Collin, Neil P King, Dan H Barouch, Darrell J Irvine, J Christopher Love
Author Information
Neil C Dalvie: Department of Chemical Engineering, Massachusetts Institute of Technology (MIT), Cambridge, MA 02139. ORCID
Sergio A Rodriguez-Aponte: The Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139.
Brittany L Hartwell: The Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139.
Lisa H Tostanoski: Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02115. ORCID
Andrew M Biedermann: Department of Chemical Engineering, Massachusetts Institute of Technology (MIT), Cambridge, MA 02139.
Laura E Crowell: Department of Chemical Engineering, Massachusetts Institute of Technology (MIT), Cambridge, MA 02139.
Kawaljit Kaur: Department of Pharmaceutical Chemistry, Vaccine Analytics, and Formulation Center, University of Kansas, Lawrence, KS 66047.
Ozan S Kumru: Department of Pharmaceutical Chemistry, Vaccine Analytics, and Formulation Center, University of Kansas, Lawrence, KS 66047.
Lauren Carter: Department of Biochemistry, University of Washington, Seattle, WA 98195.
Jingyou Yu: Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02115.
Aiquan Chang: Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02115. ORCID
Katherine McMahan: Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02115.
Thomas Courant: Vaccine Formulation Institute, 1228 Plan-Les-Ouates, Geneva, Switzerland.
Celia Lebas: Vaccine Formulation Institute, 1228 Plan-Les-Ouates, Geneva, Switzerland.
Ashley A Lemnios: The Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139. ORCID
Kristen A Rodrigues: The Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139. ORCID
Murillo Silva: The Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139.
Ryan S Johnston: The Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139.
Christopher A Naranjo: The Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139.
Mary Kate Tracey: The Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139.
Joseph R Brady: Department of Chemical Engineering, Massachusetts Institute of Technology (MIT), Cambridge, MA 02139. ORCID
Charles A Whittaker: The Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139. ORCID
Dongsoo Yun: The Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139.
Natalie Brunette: Department of Biochemistry, University of Washington, Seattle, WA 98195.
Jing Yang Wang: Department of Biochemistry, University of Washington, Seattle, WA 98195. ORCID
Carl Walkey: Department of Biochemistry, University of Washington, Seattle, WA 98195.
Brooke Fiala: Department of Biochemistry, University of Washington, Seattle, WA 98195. ORCID
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.
