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

Autor:	Dalvie NC; Department of Chemical Engineering, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA.; The Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA., Rodriguez-Aponte SA; The Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA.; Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA., Hartwell BL; The Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA.; Ragon Institute of MGH, MIT, Harvard, Cambridge, MA 02139, USA., Tostanoski LH; Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA., Biedermann AM; Department of Chemical Engineering, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA.; The Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA., Crowell LE; Department of Chemical Engineering, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA.; The Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA., Kaur K; Department of Pharmaceutical Chemistry, Vaccine Analytics and Formulation Center, University of Kansas, Lawrence, Kansas, 66047, United States., Kumru O; Department of Pharmaceutical Chemistry, Vaccine Analytics and Formulation Center, University of Kansas, Lawrence, Kansas, 66047, United States., Carter L; Department of Biochemistry, University of Washington, Seattle, WA 98195, USA.; Institute for Protein Design, University of Washington, Seattle, WA 98195, USA., Yu J; Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA., Chang A; Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA.; Harvard Medical School, Boston, MA 02115, USA., McMahan K; Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA., 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, Massachusetts 02139, USA., Rodrigues KA; The Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA.; Ragon Institute of MGH, MIT, Harvard, Cambridge, MA 02139, USA.; Harvard-MIT Health Sciences and Technology, Institute for Medical Engineering and Science, Massachusetts Institute of Technology, Cambridge, MA 02139, USA., Silva M; The Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA., Johnston RS; The Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA., Naranjo CA; The Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA., Tracey MK; The Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA., Brady JR; Department of Chemical Engineering, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA.; The Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA., Whittaker CA; The Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA., Yun D; The Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA., Kar S; Bioqual, Inc., Rockville, MD 20850, USA., Porto M; Bioqual, Inc., Rockville, MD 20850, USA., Lok M; Bioqual, Inc., Rockville, MD 20850, USA., Andersen H; Bioqual, Inc., Rockville, MD 20850, USA., Lewis MG; Bioqual, Inc., Rockville, MD 20850, USA., Love KR; Department of Chemical Engineering, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA.; The Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA., Camp DL; The Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA., Silverman JM; Bill & Melinda Gates Medical Research Institute, Cambridge, MA 02139, USA., Kleanthous H; Bill&Melinda Gates Foundation, Seattle, WA 98109, USA., Joshi SB; Department of Pharmaceutical Chemistry, Vaccine Analytics and Formulation Center, University of Kansas, Lawrence, Kansas, 66047, United States., Volkin DB; Department of Pharmaceutical Chemistry, Vaccine Analytics and Formulation Center, University of Kansas, Lawrence, Kansas, 66047, United States., 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, USA.; Institute for Protein Design, University of Washington, Seattle, WA 98195, USA., Barouch DH; Ragon Institute of MGH, MIT, Harvard, Cambridge, MA 02139, USA.; Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA.; Harvard Medical School, Boston, MA 02115, USA.; Massachusetts Consortium on Pathogen Readiness, Boston, MA 02115, USA., Irvine DJ; The Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA.; Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA.; Ragon Institute of MGH, MIT, Harvard, Cambridge, MA 02139, USA.; Howard Hughes Medical Institute, Chevy Chase, MD 20815, USA., Love JC; Department of Chemical Engineering, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA.; The Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA.
Jazyk:	angličtina
Zdroj:	BioRxiv : the preprint server for biology [bioRxiv] 2021 Mar 04. Date of Electronic Publication: 2021 Mar 04.
DOI:	10.1101/2021.03.03.433558
Abstrakt:	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. Competing Interests: Competing interests 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. 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.
Databáze:	MEDLINE
Externí odkaz:	Zobrazit plný text záznamu