Language:

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

Proceedings of the National Academy of Sciences - PNAS, 2021-09, Vol.118 (38) [Peer Reviewed Journal]

Copyright © 2021 the Author(s). Published by PNAS. ;Copyright National Academy of Sciences Sep 21, 2021 ;Copyright © 2021 the Author(s). Published by PNAS. 2021 ;ISSN: 0027-8424 ;EISSN: 1091-6490 ;DOI: 10.1073/pnas.2106845118 ;PMID: 34493582

Full text available

Citations Cited by

Actions
1. Add to My Research
2. Remove from My Research
3. E-mail
4. Print
5. Permalink
6. Citation
7. EasyBib
8. EndNote
9. RefWorks
10. Delicious
11. Export RIS
12. Export BibTeX

Title:
Engineered SARS-CoV-2 receptor binding domain improves manufacturability in yeast and immunogenicity in mice
Author: 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
Subjects: ACE2 ; Angiotensin-converting enzyme 2 ; Animals ; Antibodies ; Antibodies, Viral - immunology ; Antigens, Viral ; Binding ; Binding Sites ; Biological Sciences ; COVID-19 ; COVID-19 - prevention & control ; COVID-19 - virology ; COVID-19 Vaccines - economics ; COVID-19 Vaccines - immunology ; Domains ; Hamsters ; Humans ; Immunogenicity ; Immunogenicity, Vaccine ; Manufacturability ; Mice ; Mice, Inbred BALB C ; Microorganisms ; Models, Molecular ; Physical Sciences ; Production costs ; Protein Binding ; Protein Conformation ; Protein Engineering - methods ; Proteins ; Receptors ; Saccharomycetales - metabolism ; SARS-CoV-2 - metabolism ; Severe acute respiratory syndrome ; Severe acute respiratory syndrome coronavirus 2 ; Spike Glycoprotein, Coronavirus - genetics ; Vaccines ; Vaccines, Subunit ; Viral diseases ; Virus-like particles ; Viruses ; Weight loss ; Weight reduction ; Yeasts
Is Part Of: Proceedings of the National Academy of Sciences - PNAS, 2021-09, Vol.118 (38)
Description: 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.
Publisher: United States: National Academy of Sciences
Language: English
Identifier: ISSN: 0027-8424
EISSN: 1091-6490
DOI: 10.1073/pnas.2106845118
PMID: 34493582
Source: Geneva Foundation Free Medical Journals at publisher websites
MEDLINE
PubMed Central

Back to results list


INSPIRE LIBRARY - TON DUC THANG UNIVERSITY	(84-028) 37 755 057	Feedback
19 Nguyen Huu Tho St. Dist.7, HCM	thuvien@tdtu.edu.vn	Feedback

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

Copyright © 2021 the Author(s). Published by PNAS. ;Copyright National Academy of Sciences Sep 21, 2021 ;Copyright © 2021 the Author(s). Published by PNAS. 2021 ;ISSN: 0027-8424 ;EISSN: 1091-6490 ;DOI: 10.1073/pnas.2106845118 ;PMID: 34493582

Searching Remote Databases, Please Wait