气候变化领域集成服务门户(CCPortal): Engineered SARS-CoV-2 receptor binding domain improves manufacturability in yeast and immunogenicity in mice

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DOI	10.1073/pnas.2106845118
	Engineered SARS-CoV-2 receptor binding domain improves manufacturability in yeast and immunogenicity in mice
	Dalvie N.C.; Rodriguez-Aponte S.A.; Hartwell B.L.; Tostanoski L.H.; Biedermann A.M.; Crowell L.E.; Kaur K.; Kumru O.S.; Carter L.; Yu J.; Chang A.; McMahan K.; Courant T.; Lebas C.; Lemnios A.A.; Rodrigues K.A.; Silva M.; Johnston R.S.; Naranjo C.A.; Tracey M.K.; Brady J.R.; Whittaker C.A.; Yun D.; Brunette N.; Wang J.Y.; Walkey C.; Fiala B.; Kar S.; Porto M.; Lok M.; Andersen H.; Lewis M.G.; Love K.R.; Camp D.L.; Silverman J.M.; Kleanthous H.; Joshi S.B.; Volkin D.B.; Dubois P.M.; Collin N.; King N.P.; Barouch D.H.; Irvine D.J.; Love J.C.
发表日期	2021
ISSN	0027-8424
卷号	118 期号:38
英文摘要	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. © 2021 National Academy of Sciences. All rights reserved.
英文关键词	Manufacturability; Pichia pastoris; Protein vaccine; SARS-CoV-2
语种	英语
scopus关键词	aluminum hydroxide; angiotensin converting enzyme 2; CpG oligodeoxynucleotide; liposome; nanoparticle; protein vaccine; RBD L452K F490W; saponin; squalene; unclassified drug; coronavirus spike glycoprotein; protein binding; spike protein, SARS-CoV-2; subunit vaccine; virus antibody; virus antigen; amino acid sequence; animal experiment; animal model; antibody response; antigen binding; Article; binding affinity; body weight loss; controlled study; coronavirus disease 2019; drug formulation; female; immunogenicity; Komagataella pastoris; male; mouse; nonhuman; protein domain; protein engineering; receptor binding domain; SARS-CoV-2 (clinical isolate Wuhan/Hu-1/2019); SARS-CoV-2 variant 501Y.V2; Severe acute respiratory syndrome coronavirus 2; vaccine production; virus like agent; animal; Bagg albino mouse; binding site; budding yeast; economics; genetics; human; immunology; metabolism; molecular model; prevention and control; procedures; protein conformation; protein engineering; vaccine immunogenicity; virology; Animals; Antibodies, Viral; Antigens, Viral; Binding Sites; COVID-19; COVID-19 Vaccines; Humans; Immunogenicity, Vaccine; Mice; Mice, Inbred BALB C; Models, Molecular; Protein Binding; Protein Conformation; Protein Engineering; Saccharomycetales; SARS-CoV-2; Spike Glycoprotein, Coronavirus; Vaccines, Subunit
来源期刊	Proceedings of the National Academy of Sciences of the United States of America
文献类型	期刊论文
条目标识符	http://gcip.llas.ac.cn/handle/2XKMVOVA/238798
作者单位	Department of Chemical Engineering, Massachusetts Institute of Technology (MIT), Cambridge, MA 02139, United States; The Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139, United States; Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139, United States; Ragon Institute of Massachusetts General Hospital (MGH), MIT, Harvard, Cambridge, MA 02139, United States; Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02115, United States; Department of Pharmaceutical Chemistry, Vaccine Analytics, Formulation Center, University of Kansas, Lawrence, KS 66047, United States; Department of Biochemistry, University of Washington, Seattle, WA 98195, United States; Institute for Protein Design, University of Washington, Seattle, WA 98195, United States; Vaccine Formulation Institute, Plan-Les-Ouates, Geneva, 1228, Switzerland; Harvard-MIT Health Sci...
推荐引用方式 GB/T 7714	Dalvie N.C.,Rodriguez-Aponte S.A.,Hartwell B.L.,et al. Engineered SARS-CoV-2 receptor binding domain improves manufacturability in yeast and immunogenicity in mice[J],2021,118(38).
APA	Dalvie N.C..,Rodriguez-Aponte S.A..,Hartwell B.L..,Tostanoski L.H..,Biedermann A.M..,...&Love J.C..(2021).Engineered SARS-CoV-2 receptor binding domain improves manufacturability in yeast and immunogenicity in mice.Proceedings of the National Academy of Sciences of the United States of America,118(38).
MLA	Dalvie N.C.,et al."Engineered SARS-CoV-2 receptor binding domain improves manufacturability in yeast and immunogenicity in mice".Proceedings of the National Academy of Sciences of the United States of America 118.38(2021).