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Engineered SARS-CoV-2 receptor binding domain improves manufacturability in yeast and immunogenicity in mice.
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.
  • Dalvie NC; Department of Chemical Engineering, Massachusetts Institute of Technology (MIT), Cambridge, MA 02139.
  • Rodriguez-Aponte SA; The Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139.
  • Hartwell BL; The Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139.
  • Tostanoski LH; Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139.
  • Biedermann AM; The Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139.
  • Crowell LE; Ragon Institute of Massachusetts General Hospital (MGH), MIT, Harvard, Cambridge, MA 02139.
  • Kaur K; Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02115.
  • Kumru OS; Department of Chemical Engineering, Massachusetts Institute of Technology (MIT), Cambridge, MA 02139.
  • Carter L; The Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139.
  • Yu J; Department of Chemical Engineering, Massachusetts Institute of Technology (MIT), Cambridge, MA 02139.
  • Chang A; The Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139.
  • McMahan K; Department of Pharmaceutical Chemistry, Vaccine Analytics, and Formulation Center, University of Kansas, Lawrence, KS 66047.
  • Courant T; Department of Pharmaceutical Chemistry, Vaccine Analytics, and Formulation Center, University of Kansas, Lawrence, KS 66047.
  • Lebas C; Department of Biochemistry, University of Washington, Seattle, WA 98195.
  • Lemnios AA; Institute for Protein Design, University of Washington, Seattle, WA 98195.
  • Rodrigues KA; Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02115.
  • Silva M; Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02115.
  • Johnston RS; Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02115.
  • Naranjo CA; Vaccine Formulation Institute, 1228 Plan-Les-Ouates, Geneva, Switzerland.
  • Tracey MK; Vaccine Formulation Institute, 1228 Plan-Les-Ouates, Geneva, Switzerland.
  • Brady JR; The Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139.
  • Whittaker CA; The Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139.
  • Yun D; Ragon Institute of Massachusetts General Hospital (MGH), MIT, Harvard, Cambridge, MA 02139.
  • Brunette N; Harvard-MIT Health Sciences and Technology, Institute for Medical Engineering and Science, Massachusetts Institute of Technology, Cambridge, MA 02139.
  • Wang JY; The Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139.
  • Walkey C; The Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139.
  • Fiala B; The Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139.
  • Kar S; The Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139.
  • Porto M; Department of Chemical Engineering, Massachusetts Institute of Technology (MIT), Cambridge, MA 02139.
  • Lok M; The Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139.
  • Andersen H; The Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139.
  • Lewis MG; The Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139.
  • Love KR; Department of Biochemistry, University of Washington, Seattle, WA 98195.
  • Camp DL; Institute for Protein Design, University of Washington, Seattle, WA 98195.
  • Silverman JM; Department of Biochemistry, University of Washington, Seattle, WA 98195.
  • Kleanthous H; Institute for Protein Design, University of Washington, Seattle, WA 98195.
  • Joshi SB; Department of Biochemistry, University of Washington, Seattle, WA 98195.
  • Volkin DB; Institute for Protein Design, University of Washington, Seattle, WA 98195.
  • Dubois PM; Department of Biochemistry, University of Washington, Seattle, WA 98195.
  • Collin N; Institute for Protein Design, University of Washington, Seattle, WA 98195.
  • King NP; Bioqual, Inc., Rockville, MD 20850.
  • Barouch DH; Bioqual, Inc., Rockville, MD 20850.
  • Irvine DJ; Bioqual, Inc., Rockville, MD 20850.
  • Love JC; Bioqual, Inc., Rockville, MD 20850.
Proc Natl Acad Sci U S A ; 118(38)2021 09 21.
Article in English | MEDLINE | ID: covidwho-1397979
ABSTRACT
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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Full text: Available Collection: International databases Database: MEDLINE Main subject: Protein Engineering / Spike Glycoprotein, Coronavirus / COVID-19 Vaccines / SARS-CoV-2 / COVID-19 Topics: Vaccines / Variants Limits: Animals / Humans Language: English Year: 2021 Document Type: Article

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Full text: Available Collection: International databases Database: MEDLINE Main subject: Protein Engineering / Spike Glycoprotein, Coronavirus / COVID-19 Vaccines / SARS-CoV-2 / COVID-19 Topics: Vaccines / Variants Limits: Animals / Humans Language: English Year: 2021 Document Type: Article