Engineered SARS-CoV-2 receptor binding domain improves manufacturability in yeast and immunogenicity in mice.

Autor:	Dalvie NC; Department of Chemical Engineering, Massachusetts Institute of Technology (MIT), Cambridge, MA 02139.; The Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139., Rodriguez-Aponte SA; The Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139.; Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139., Hartwell BL; The Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139.; Ragon Institute of Massachusetts General Hospital (MGH), MIT, Harvard, Cambridge, MA 02139., Tostanoski LH; Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02115., Biedermann AM; Department of Chemical Engineering, Massachusetts Institute of Technology (MIT), Cambridge, MA 02139.; The Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139., Crowell LE; Department of Chemical Engineering, Massachusetts Institute of Technology (MIT), Cambridge, MA 02139.; The Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139., Kaur K; Department of Pharmaceutical Chemistry, Vaccine Analytics, and Formulation Center, University of Kansas, Lawrence, KS 66047., Kumru OS; Department of Pharmaceutical Chemistry, Vaccine Analytics, and Formulation Center, University of Kansas, Lawrence, KS 66047., Carter L; Department of Biochemistry, University of Washington, Seattle, WA 98195.; Institute for Protein Design, University of Washington, Seattle, WA 98195., Yu J; Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02115., Chang A; Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02115., McMahan K; Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02115., Courant T; Vaccine Formulation Institute, 1228 Plan-Les-Ouates, Geneva, Switzerland., Lebas C; Vaccine Formulation Institute, 1228 Plan-Les-Ouates, Geneva, Switzerland., Lemnios AA; The Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139., Rodrigues KA; The Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139.; Ragon Institute of Massachusetts General Hospital (MGH), MIT, Harvard, Cambridge, MA 02139.; Harvard-MIT Health Sciences and Technology, Institute for Medical Engineering and Science, Massachusetts Institute of Technology, Cambridge, MA 02139., Silva M; The Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139., Johnston RS; The Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139., Naranjo CA; The Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139., Tracey MK; The Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139., Brady JR; Department of Chemical Engineering, Massachusetts Institute of Technology (MIT), Cambridge, MA 02139.; 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; The Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139., Brunette N; Department of Biochemistry, University of Washington, Seattle, WA 98195.; Institute for Protein Design, University of Washington, Seattle, WA 98195., Wang JY; Department of Biochemistry, University of Washington, Seattle, WA 98195.; Institute for Protein Design, University of Washington, Seattle, WA 98195., Walkey C; Department of Biochemistry, University of Washington, Seattle, WA 98195.; Institute for Protein Design, University of Washington, Seattle, WA 98195., Fiala B; Department of Biochemistry, University of Washington, Seattle, WA 98195.; Institute for Protein Design, University of Washington, Seattle, WA 98195., Kar S; Bioqual, Inc., Rockville, MD 20850., Porto M; Bioqual, Inc., Rockville, MD 20850., Lok M; Bioqual, Inc., Rockville, MD 20850., Andersen H; Bioqual, Inc., Rockville, MD 20850., Lewis MG; Bioqual, Inc., Rockville, MD 20850., Love KR; Department of Chemical Engineering, Massachusetts Institute of Technology (MIT), Cambridge, MA 02139.; The Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139., Camp DL; The Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139., Silverman JM; Bill & Melinda Gates Medical Research Institute, Cambridge, MA 02139., Kleanthous H; Bill & Melinda Gates Foundation, Seattle, WA 98109., Joshi SB; Department of Pharmaceutical Chemistry, Vaccine Analytics, and Formulation Center, University of Kansas, Lawrence, KS 66047., Volkin DB; Department of Pharmaceutical Chemistry, Vaccine Analytics, and Formulation Center, University of Kansas, Lawrence, KS 66047., Dubois PM; Vaccine Formulation Institute, 1228 Plan-Les-Ouates, Geneva, Switzerland., Collin N; Vaccine Formulation Institute, 1228 Plan-Les-Ouates, Geneva, Switzerland., King NP; Department of Biochemistry, University of Washington, Seattle, WA 98195.; Institute for Protein Design, University of Washington, Seattle, WA 98195., Barouch DH; Ragon Institute of Massachusetts General Hospital (MGH), MIT, Harvard, Cambridge, MA 02139.; Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02115.; Massachusetts Consortium on Pathogen Readiness, Boston, MA 02115., Irvine DJ; The Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139.; Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139.; Ragon Institute of Massachusetts General Hospital (MGH), MIT, Harvard, Cambridge, MA 02139.; Howard Hughes Medical Institute, Chevy Chase, MD 20815., Love JC; Department of Chemical Engineering, Massachusetts Institute of Technology (MIT), Cambridge, MA 02139; clove@mit.edu.; The Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139.
Jazyk:	angličtina
Zdroj:	Proceedings of the National Academy of Sciences of the United States of America [Proc Natl Acad Sci U S A] 2021 Sep 21; Vol. 118 (38).
DOI:	10.1073/pnas.2106845118
Abstrakt:	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. Competing Interests: Competing interest statement: L.E.C., K.R.L., and J.C.L. have filed patents related to the InSCyT system and methods. N.C.D., S.R.A., and J.C.L. have filed a patent related to the RBD-L452K-F490W sequence. K.R.L., L.E.C., and M.K.T. are current employees at Sunflower Therapeutics PBC. N.P.K., J.Y.W., and C.W. are named as inventors on patent applications filed by the University of Washington related to the I3-01 nanoparticle. N.P.K. is a co-founder, shareholder, paid consultant, and chair of the scientific advisory board of Icosavax, Inc. and has received an unrelated sponsored research agreement from Pfizer. J.C.L. has interests in Sunflower Therapeutics PBC, Pfizer, Honeycomb Biotechnologies, OneCyte Biotechnologies, QuantumCyte, Amgen, and Repligen. J.C.L.’s interests are reviewed and managed under MIT’s policies for potential conflicts of interest. J.M.S. is an employee of the Bill & Melinda Gates Medical Research Institute. H.K. is an employee of the Bill & Melinda Gates Foundation. (Copyright © 2021 the Author(s). Published by PNAS.)
Databáze:	MEDLINE
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