Engineered SARS-CoV-2 receptor binding domain improves manufacturability in yeast and immunogenicity in mice
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 l...
Saved in:
| Published in | Proceedings of the National Academy of Sciences - PNAS Vol. 118; no. 38; pp. 1 - 9 |
|---|---|
| Main Authors | , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , |
| Format | Journal Article |
| Language | English |
| Published |
United States
National Academy of Sciences
21.09.2021
|
| Subjects | |
| Online Access | Get full text |
| ISSN | 0027-8424 1091-6490 1091-6490 |
| DOI | 10.1073/pnas.2106845118 |
Cover
Loading…
| 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. |
|---|---|
| AbstractList | 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. Most of the global population resides in low- and middle-income countries, where current vaccines for COVID-19 remain largely unavailable. For the COVID-19 pandemic, the world will need access to >10 billion doses of vaccines, or more than double the annual volume of vaccines for all other diseases. Many vaccine candidates use the SARS-CoV-2 receptor-binding domain (RBD) antigen. Here, we present an engineered RBD with improved production titers in Pichia pastoris , a yeast commonly used for large-scale, low-cost manufacturing by vaccine manufacturers. The modified RBD also raises an enhanced immune response in mice relative to the Wuhan-Hu-1 sequence used in current candidates. These combined traits make it a promising candidate for next-generation vaccines addressing emerging variants of the virus. 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. 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.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. |
| Author | Hartwell, Brittany L. Silva, Murillo Yun, Dongsoo Rodrigues, Kristen A. Tracey, Mary Kate Porto, Maciel King, Neil P. Volkin, David B. Irvine, Darrell J. Silverman, Judith Maxwell Johnston, Ryan S. Brunette, Natalie Kaur, Kawaljit Chang, Aiquan Lemnios, Ashley A. Naranjo, Christopher A. Kumru, Ozan S. Love, J. Christopher Rodriguez-Aponte, Sergio A. Yu, Jingyou Whittaker, Charles A. Lebas, Celia Carter, Lauren Fiala, Brooke Love, Kerry R. Barouch, Dan H. Biedermann, Andrew M. Camp, Danielle L. Wang, Jing Yang Dubois, Patrice M. Andersen, Hanne Lewis, Mark G. Lok, Megan Joshi, Sangeeta B. Brady, Joseph R. Walkey, Carl Kleanthous, Harry Dalvie, Neil C. Kar, Swagata Courant, Thomas Collin, Nicolas Crowell, Laura E. McMahan, Katherine Tostanoski, Lisa H. |
| Author_xml | – sequence: 1 givenname: Neil C. surname: Dalvie fullname: Dalvie, Neil C. – sequence: 2 givenname: Sergio A. surname: Rodriguez-Aponte fullname: Rodriguez-Aponte, Sergio A. – sequence: 3 givenname: Brittany L. surname: Hartwell fullname: Hartwell, Brittany L. – sequence: 4 givenname: Lisa H. surname: Tostanoski fullname: Tostanoski, Lisa H. – sequence: 5 givenname: Andrew M. surname: Biedermann fullname: Biedermann, Andrew M. – sequence: 6 givenname: Laura E. surname: Crowell fullname: Crowell, Laura E. – sequence: 7 givenname: Kawaljit surname: Kaur fullname: Kaur, Kawaljit – sequence: 8 givenname: Ozan S. surname: Kumru fullname: Kumru, Ozan S. – sequence: 9 givenname: Lauren surname: Carter fullname: Carter, Lauren – sequence: 10 givenname: Jingyou surname: Yu fullname: Yu, Jingyou – sequence: 11 givenname: Aiquan surname: Chang fullname: Chang, Aiquan – sequence: 12 givenname: Katherine surname: McMahan fullname: McMahan, Katherine – sequence: 13 givenname: Thomas surname: Courant fullname: Courant, Thomas – sequence: 14 givenname: Celia surname: Lebas fullname: Lebas, Celia – sequence: 15 givenname: Ashley A. surname: Lemnios fullname: Lemnios, Ashley A. – sequence: 16 givenname: Kristen A. surname: Rodrigues fullname: Rodrigues, Kristen A. – sequence: 17 givenname: Murillo surname: Silva fullname: Silva, Murillo – sequence: 18 givenname: Ryan S. surname: Johnston fullname: Johnston, Ryan S. – sequence: 19 givenname: Christopher A. surname: Naranjo fullname: Naranjo, Christopher A. – sequence: 20 givenname: Mary Kate surname: Tracey fullname: Tracey, Mary Kate – sequence: 21 givenname: Joseph R. surname: Brady fullname: Brady, Joseph R. – sequence: 22 givenname: Charles A. surname: Whittaker fullname: Whittaker, Charles A. – sequence: 23 givenname: Dongsoo surname: Yun fullname: Yun, Dongsoo – sequence: 24 givenname: Natalie surname: Brunette fullname: Brunette, Natalie – sequence: 25 givenname: Jing Yang surname: Wang fullname: Wang, Jing Yang – sequence: 26 givenname: Carl surname: Walkey fullname: Walkey, Carl – sequence: 27 givenname: Brooke surname: Fiala fullname: Fiala, Brooke – sequence: 28 givenname: Swagata surname: Kar fullname: Kar, Swagata – sequence: 29 givenname: Maciel surname: Porto fullname: Porto, Maciel – sequence: 30 givenname: Megan surname: Lok fullname: Lok, Megan – sequence: 31 givenname: Hanne surname: Andersen fullname: Andersen, Hanne – sequence: 32 givenname: Mark G. surname: Lewis fullname: Lewis, Mark G. – sequence: 33 givenname: Kerry R. surname: Love fullname: Love, Kerry R. – sequence: 34 givenname: Danielle L. surname: Camp fullname: Camp, Danielle L. – sequence: 35 givenname: Judith Maxwell surname: Silverman fullname: Silverman, Judith Maxwell – sequence: 36 givenname: Harry surname: Kleanthous fullname: Kleanthous, Harry – sequence: 37 givenname: Sangeeta B. surname: Joshi fullname: Joshi, Sangeeta B. – sequence: 38 givenname: David B. surname: Volkin fullname: Volkin, David B. – sequence: 39 givenname: Patrice M. surname: Dubois fullname: Dubois, Patrice M. – sequence: 40 givenname: Nicolas surname: Collin fullname: Collin, Nicolas – sequence: 41 givenname: Neil P. surname: King fullname: King, Neil P. – sequence: 42 givenname: Dan H. surname: Barouch fullname: Barouch, Dan H. – sequence: 43 givenname: Darrell J. surname: Irvine fullname: Irvine, Darrell J. – sequence: 44 givenname: J. Christopher surname: Love fullname: Love, J. Christopher |
| BackLink | https://www.ncbi.nlm.nih.gov/pubmed/34493582$$D View this record in MEDLINE/PubMed |
| BookMark | eNp1kU1r3DAYhEVJaTbbnntqMeSSixNZn9alEJY0LQQKTehVyPLrrRZbciU7sP--MrtJ20APQod5ZhhpztCJDx4Qel_hywpLejV6ky5JhUXNeFXVr9CqwqoqBVP4BK0wJrKsGWGn6CylHcZY8Rq_QaeUMUV5TVaov_Fb5wEitMX99ff7chN-lKSIYGGcQiwa51vnt0UbBuN84YYxhkdIxWD83Bk7zdE0rnfTvsjqHkyaCuPbzA2zD1vwzh61wVl4i153pk_w7niv0cPnm4fNl_Lu2-3XzfVdaTlWUwmyVozntm1dE9PiTrVQgWUdYDCEtZyCEKLiHbNUSIpFo5hUDbegjGkIXaNPh9hxbgZoLfgpml6P0Q0m7nUwTv-rePdTb8Ojrpmgy1mji2NADL9mSJMeXLLQ98ZDmJMmXGIqKZMLev4C3YU5-vy6hRJUCE5Upj7-3ei5ytMOGeAHwMaQUoRO538zkwtLQdfrCutlb73srf_snX1XL3xP0f93fDg4dinv-4wTiSXPdelvI3e4kQ |
| CitedBy_id | crossref_primary_10_1371_journal_ppat_1012487 crossref_primary_10_1002_bit_28385 crossref_primary_10_1080_17425247_2023_2189697 crossref_primary_10_3390_fermentation9060497 crossref_primary_10_1002_bit_27979 crossref_primary_10_3389_fimmu_2022_948431 crossref_primary_10_3390_vaccines11040832 crossref_primary_10_3389_fpls_2022_988870 crossref_primary_10_1038_s41467_024_44869_0 crossref_primary_10_3389_fimmu_2023_1204834 crossref_primary_10_1038_s41541_022_00450_8 crossref_primary_10_1016_j_celrep_2023_113552 crossref_primary_10_1038_s41467_023_42200_x crossref_primary_10_1080_21645515_2023_2264594 crossref_primary_10_1016_j_btre_2022_e00780 crossref_primary_10_1126_sciadv_abl6015 crossref_primary_10_3390_vaccines11101602 crossref_primary_10_1002_anbr_202400077 crossref_primary_10_1016_j_crmeth_2022_100273 crossref_primary_10_1002_bit_28878 crossref_primary_10_1186_s12934_022_01905_2 crossref_primary_10_3389_fimmu_2022_1015840 crossref_primary_10_3389_fbioe_2022_1052436 crossref_primary_10_3390_vaccines11061030 crossref_primary_10_1016_j_vaccine_2022_12_062 crossref_primary_10_3389_fbioe_2023_1287551 crossref_primary_10_1016_j_ijbiomac_2022_04_096 crossref_primary_10_3390_bios12121133 crossref_primary_10_1021_acssynbio_1c00194 crossref_primary_10_1016_j_pep_2022_106075 crossref_primary_10_3389_fimmu_2023_1188605 crossref_primary_10_1016_j_jconrel_2024_12_054 crossref_primary_10_1016_j_celrep_2024_115036 crossref_primary_10_1080_14760584_2023_2211153 crossref_primary_10_1126_scitranslmed_abj5305 crossref_primary_10_1021_acsomega_3c01625 crossref_primary_10_3389_fpls_2023_1275228 crossref_primary_10_1016_j_nbt_2022_08_002 crossref_primary_10_3390_v14122794 crossref_primary_10_3389_fimmu_2022_844837 crossref_primary_10_3390_v15020392 crossref_primary_10_1128_spectrum_04998_22 crossref_primary_10_1007_s12275_022_1608_z crossref_primary_10_1128_msphere_00243_22 crossref_primary_10_1038_s41467_022_35606_6 crossref_primary_10_1093_protein_gzac002 crossref_primary_10_1038_s41541_021_00393_6 crossref_primary_10_1016_j_pep_2024_106556 crossref_primary_10_1021_acschembio_2c00140 crossref_primary_10_1126_scitranslmed_abn1413 crossref_primary_10_1038_s41541_023_00610_4 crossref_primary_10_1073_pnas_2214556120 crossref_primary_10_1186_s12896_023_00777_7 crossref_primary_10_1126_sciadv_adn7786 |
| Cites_doi | 10.1016/j.cell.2021.03.029 10.1038/nbt.4262 10.1038/s41586-020-2380-z 10.1056/NEJMoa2035389 10.1126/science.abc5902 10.1126/science.abf6840 10.1128/JVI.00127-20 10.1016/S2213-2600(21)00075-8 10.1016/j.vaccine.2011.07.128 10.1016/j.chembiol.2008.03.002 10.1016/j.chom.2021.02.003 10.4161/hv.27464 10.12688/f1000research.7563.1 10.1128/jvi.00404-21 10.1038/nature20108 10.1038/s41467-021-21665-8 10.1002/bit.27209 10.1126/sciimmunol.abj1750 10.1016/j.cell.2021.02.032 10.1021/acssynbio.9b00372 10.1186/s13059-014-0550-8 10.1073/pnas.0506580102 10.1038/s41467-020-20654-7 10.1186/s12934-021-01583-6 10.1038/s41586-021-03594-0 10.1016/j.cell.2020.02.058 10.1128/mBio.00122-20 10.1101/gr.849004 10.1016/j.cbpa.2015.10.002 10.1021/acsnano.0c08379 10.1038/s41586-020-2599-8 10.1001/jama.2021.1114 10.1080/21645515.2021.1901545 10.1038/nmeth.4197 10.1080/21645515.2020.1740560 10.1016/j.cell.2021.06.020 10.1056/NEJMp2003762 10.1002/bit.27724 10.1056/NEJMoa1501184 10.1016/j.xcrm.2021.100255 10.1056/NEJMoa2034577 10.1016/j.vaccine.2020.10.064 10.1016/j.chom.2020.11.007 10.1007/s00253-015-6470-z 10.1002/prot.25594 10.1038/s41586-020-2179-y 10.1126/science.abg8985 10.1038/s41586-020-2607-z 10.1093/bioinformatics/btp616 10.1016/j.xphs.2017.04.037 10.1126/science.abc4776 10.1080/21645515.2017.1289301 10.1093/nar/gks042 10.1126/science.abc6284 10.1080/22221751.2020.1729069 10.1038/nature02463 10.1038/s41541-020-0187-4 10.1155/2019/6491738 10.1016/j.virol.2009.07.018 10.1056/NEJMoa2103055 10.1002/btpr.2966 10.1038/s41591-021-01318-5 10.1101/2021.01.04.425316 10.1038/ncomms8712 10.1016/j.cell.2020.10.043 10.1038/d41586-020-03134-2 10.1016/j.jmb.2005.11.035 10.1016/j.vaccine.2017.05.054 |
| ContentType | Journal Article |
| Copyright | 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 |
| Copyright_xml | – notice: Copyright © 2021 the Author(s). Published by PNAS. – notice: Copyright National Academy of Sciences Sep 21, 2021 – notice: Copyright © 2021 the Author(s). Published by PNAS. 2021 |
| DBID | AAYXX CITATION CGR CUY CVF ECM EIF NPM 7QG 7QL 7QP 7QR 7SN 7SS 7T5 7TK 7TM 7TO 7U9 8FD C1K FR3 H94 M7N P64 RC3 7X8 5PM |
| DOI | 10.1073/pnas.2106845118 |
| DatabaseName | CrossRef Medline MEDLINE MEDLINE (Ovid) MEDLINE MEDLINE PubMed Animal Behavior Abstracts Bacteriology Abstracts (Microbiology B) Calcium & Calcified Tissue Abstracts Chemoreception Abstracts Ecology Abstracts Entomology Abstracts (Full archive) Immunology Abstracts Neurosciences Abstracts Nucleic Acids Abstracts Oncogenes and Growth Factors Abstracts Virology and AIDS Abstracts Technology Research Database Environmental Sciences and Pollution Management Engineering Research Database AIDS and Cancer Research Abstracts Algology Mycology and Protozoology Abstracts (Microbiology C) Biotechnology and BioEngineering Abstracts Genetics Abstracts MEDLINE - Academic PubMed Central (Full Participant titles) |
| DatabaseTitle | CrossRef MEDLINE Medline Complete MEDLINE with Full Text PubMed MEDLINE (Ovid) Virology and AIDS Abstracts Oncogenes and Growth Factors Abstracts Technology Research Database Nucleic Acids Abstracts Ecology Abstracts Neurosciences Abstracts Biotechnology and BioEngineering Abstracts Environmental Sciences and Pollution Management Entomology Abstracts Genetics Abstracts Animal Behavior Abstracts Bacteriology Abstracts (Microbiology B) Algology Mycology and Protozoology Abstracts (Microbiology C) AIDS and Cancer Research Abstracts Chemoreception Abstracts Immunology Abstracts Engineering Research Database Calcium & Calcified Tissue Abstracts MEDLINE - Academic |
| DatabaseTitleList | MEDLINE CrossRef MEDLINE - Academic Virology and AIDS Abstracts |
| Database_xml | – sequence: 1 dbid: NPM name: PubMed url: https://proxy.k.utb.cz/login?url=http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed sourceTypes: Index Database – sequence: 2 dbid: EIF name: MEDLINE url: https://proxy.k.utb.cz/login?url=https://www.webofscience.com/wos/medline/basic-search sourceTypes: Index Database |
| DeliveryMethod | fulltext_linktorsrc |
| Discipline | Sciences (General) |
| EISSN | 1091-6490 |
| EndPage | 9 |
| ExternalDocumentID | PMC8463846 34493582 10_1073_pnas_2106845118 27075636 |
| Genre | Research Support, Non-U.S. Gov't Journal Article Research Support, N.I.H., Extramural |
| GrantInformation_xml | – fundername: NIAID NIH HHS grantid: T32 AI007387 – fundername: NCI NIH HHS grantid: P30 CA014051 – fundername: HHS | National Institutes of Health (NIH) grantid: T32 AI007387 – fundername: Bill and Melinda Gates Foundation (Bill & Melinda Gates Foundation) grantid: INV-006131 – fundername: Bill and Melinda Gates Foundation (Bill & Melinda Gates Foundation) grantid: OPP1156262 – fundername: Bill and Melinda Gates Foundation (Bill & Melinda Gates Foundation) grantid: INV-002740 |
| GroupedDBID | --- -DZ -~X .55 0R~ 123 29P 2AX 2FS 2WC 4.4 53G 5RE 5VS 85S AACGO AAFWJ AANCE ABBHK ABOCM ABPLY ABPPZ ABTLG ABXSQ ABZEH ACGOD ACIWK ACNCT ACPRK AENEX AEUPB AEXZC AFFNX AFOSN AFRAH ALMA_UNASSIGNED_HOLDINGS BKOMP CS3 D0L DCCCD DIK DU5 E3Z EBS F5P FRP GX1 H13 HH5 HYE IPSME JAAYA JBMMH JENOY JHFFW JKQEH JLS JLXEF JPM JSG JST KQ8 L7B LU7 N9A N~3 O9- OK1 PNE PQQKQ R.V RHI RNA RNS RPM RXW SA0 SJN TAE TN5 UKR W8F WH7 WOQ WOW X7M XSW Y6R YBH YKV YSK ZCA ~02 ~KM AAYXX CITATION CGR CUY CVF ECM EIF NPM 7QG 7QL 7QP 7QR 7SN 7SS 7T5 7TK 7TM 7TO 7U9 8FD C1K FR3 H94 M7N P64 RC3 7X8 5PM |
| ID | FETCH-LOGICAL-c509t-e78945000d882ad0f9de1ec4fe0ea24d53e66615f4c367306b9479b5ce9aab23 |
| ISSN | 0027-8424 1091-6490 |
| IngestDate | Thu Aug 21 14:06:02 EDT 2025 Fri Jul 11 16:43:35 EDT 2025 Mon Jun 30 10:00:37 EDT 2025 Thu Apr 03 06:59:50 EDT 2025 Tue Jul 01 01:03:03 EDT 2025 Thu Apr 24 23:01:19 EDT 2025 Thu May 29 08:53:13 EDT 2025 |
| IsDoiOpenAccess | true |
| IsOpenAccess | true |
| IsPeerReviewed | true |
| IsScholarly | true |
| Issue | 38 |
| Keywords | SARS-CoV-2 Pichia pastoris manufacturability protein vaccine |
| Language | English |
| License | Copyright © 2021 the Author(s). Published by PNAS. This open access article is distributed under Creative Commons Attribution License 4.0 (CC BY). |
| LinkModel | OpenURL |
| MergedId | FETCHMERGED-LOGICAL-c509t-e78945000d882ad0f9de1ec4fe0ea24d53e66615f4c367306b9479b5ce9aab23 |
| Notes | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 14 content type line 23 4Present address: Neoleukin Therapeutics, Seattle, WA 98102. Author contributions: N.C.D., S.A.R.-A., B.L.H., L.H.T., K.K., O.S.K., K.R.L., D.L.C., J.M.S., H.K., S.B.J., D.B.V., P.M.D., N.C., N.P.K., D.H.B., D.J.I., and J.C.L. designed research; N.C.D., S.A.R.-A., B.L.H., L.H.T., A.M.B., L.E.C., K.K., O.S.K., J.Y., A.C., K.M., T.C., C.L., A.A.L., K.A.R., R.S.J., C.A.N., M.K.T., J.R.B., C.A.W., D.Y., N.B., J.Y.W., C.W., B.F., S.K., M.P., M.L., H.A., M.G.L., and N.C. performed research; B.L.H., L.H.T., K.K., O.S.K., L.C., J.Y., A.C., K.M., M.S., N.B., J.Y.W., C.W., B.F., S.B.J., D.B.V., and N.P.K. contributed new reagents/analytic tools; N.C.D., S.A.R.-A., B.L.H., L.H.T., A.M.B., K.K., O.S.K., J.Y., A.C., K.M., C.A.N., J.R.B., C.A.W., D.Y., K.R.L., S.B.J., D.B.V., P.M.D., N.C., D.H.B., D.J.I., and J.C.L. analyzed data; and N.C.D., S.A.R.-A., B.L.H., L.H.T., K.R.L., and J.C.L. wrote the paper. 3Present address: Flagship Pioneering, Cambridge, MA 02142. 2Present address: Sunflower Therapeutics, PBC, Hingham, MA, 02043. 5Present address: Icosavax Inc., Seattle, WA 98102. Edited by Matthew V. Tirrell, The University of Chicago, Chicago, IL, and approved July 21, 2021 (received for review April 10, 2021) 1N.C.D. and S.A.R.-A. contributed equally to this work. |
| ORCID | 0000-0001-9255-5684 0000-0002-2284-3872 0000-0002-1511-6976 0000-0001-7852-0135 0000-0002-9482-0979 0000-0002-2400-0094 0000-0003-0921-3144 0000-0003-0148-5268 0000-0002-0680-9834 0000-0002-8637-1405 0000-0002-6866-6867 0000-0002-7128-9396 0000-0002-7912-0309 |
| OpenAccessLink | https://pubmed.ncbi.nlm.nih.gov/PMC8463846 |
| PMID | 34493582 |
| PQID | 2576366529 |
| PQPubID | 42026 |
| PageCount | 9 |
| ParticipantIDs | pubmedcentral_primary_oai_pubmedcentral_nih_gov_8463846 proquest_miscellaneous_2570373476 proquest_journals_2576366529 pubmed_primary_34493582 crossref_citationtrail_10_1073_pnas_2106845118 crossref_primary_10_1073_pnas_2106845118 jstor_primary_27075636 |
| ProviderPackageCode | CITATION AAYXX |
| PublicationCentury | 2000 |
| PublicationDate | 2021-09-21 |
| PublicationDateYYYYMMDD | 2021-09-21 |
| PublicationDate_xml | – month: 09 year: 2021 text: 2021-09-21 day: 21 |
| PublicationDecade | 2020 |
| PublicationPlace | United States |
| PublicationPlace_xml | – name: United States – name: Washington |
| PublicationTitle | Proceedings of the National Academy of Sciences - PNAS |
| PublicationTitleAlternate | Proc Natl Acad Sci U S A |
| PublicationYear | 2021 |
| Publisher | National Academy of Sciences |
| Publisher_xml | – name: National Academy of Sciences |
| References | e_1_3_4_3_2 e_1_3_4_1_2 e_1_3_4_61_2 e_1_3_4_9_2 e_1_3_4_63_2 e_1_3_4_7_2 e_1_3_4_40_2 e_1_3_4_5_2 e_1_3_4_23_2 e_1_3_4_44_2 e_1_3_4_21_2 e_1_3_4_42_2 e_1_3_4_27_2 e_1_3_4_48_2 e_1_3_4_65_2 e_1_3_4_25_2 e_1_3_4_46_2 e_1_3_4_67_2 e_1_3_4_29_2 e_1_3_4_30_2 e_1_3_4_51_2 e_1_3_4_11_2 e_1_3_4_34_2 e_1_3_4_57_2 e_1_3_4_55_2 e_1_3_4_32_2 e_1_3_4_59_2 e_1_3_4_53_2 e_1_3_4_15_2 e_1_3_4_38_2 e_1_3_4_13_2 e_1_3_4_36_2 e_1_3_4_19_2 e_1_3_4_17_2 e_1_3_4_2_2 e_1_3_4_60_2 e_1_3_4_62_2 e_1_3_4_8_2 e_1_3_4_41_2 e_1_3_4_6_2 e_1_3_4_4_2 e_1_3_4_22_2 e_1_3_4_45_2 e_1_3_4_68_2 e_1_3_4_20_2 e_1_3_4_43_2 e_1_3_4_26_2 e_1_3_4_49_2 e_1_3_4_64_2 e_1_3_4_24_2 e_1_3_4_47_2 e_1_3_4_66_2 e_1_3_4_28_2 e_1_3_4_52_2 e_1_3_4_50_2 e_1_3_4_12_2 e_1_3_4_33_2 e_1_3_4_58_2 e_1_3_4_54_2 e_1_3_4_10_2 e_1_3_4_31_2 e_1_3_4_16_2 e_1_3_4_37_2 e_1_3_4_14_2 e_1_3_4_35_2 e_1_3_4_56_2 e_1_3_4_18_2 e_1_3_4_39_2 33688647 - bioRxiv. 2021 Mar 04:2021.03.03.433558. doi: 10.1101/2021.03.03.433558 |
| References_xml | – ident: e_1_3_4_52_2 doi: 10.1016/j.cell.2021.03.029 – ident: e_1_3_4_21_2 doi: 10.1038/nbt.4262 – ident: e_1_3_4_14_2 doi: 10.1038/s41586-020-2380-z – ident: e_1_3_4_5_2 doi: 10.1056/NEJMoa2035389 – ident: e_1_3_4_33_2 doi: 10.1126/science.abc5902 – ident: e_1_3_4_10_2 doi: 10.1126/science.abf6840 – ident: e_1_3_4_28_2 doi: 10.1128/JVI.00127-20 – ident: e_1_3_4_37_2 doi: 10.1016/S2213-2600(21)00075-8 – ident: e_1_3_4_9_2 doi: 10.1016/j.vaccine.2011.07.128 – ident: e_1_3_4_3_2 doi: 10.1016/j.chembiol.2008.03.002 – ident: e_1_3_4_15_2 doi: 10.1016/j.chom.2021.02.003 – ident: e_1_3_4_20_2 doi: 10.4161/hv.27464 – ident: e_1_3_4_59_2 doi: 10.12688/f1000research.7563.1 – ident: e_1_3_4_34_2 doi: 10.1128/jvi.00404-21 – ident: e_1_3_4_43_2 doi: 10.1038/nature20108 – ident: e_1_3_4_54_2 doi: 10.1038/s41467-021-21665-8 – ident: e_1_3_4_56_2 doi: 10.1002/bit.27209 – ident: e_1_3_4_45_2 doi: 10.1126/sciimmunol.abj1750 – ident: e_1_3_4_48_2 doi: 10.1016/j.cell.2021.02.032 – ident: e_1_3_4_57_2 doi: 10.1021/acssynbio.9b00372 – ident: e_1_3_4_62_2 doi: 10.1186/s13059-014-0550-8 – ident: e_1_3_4_63_2 doi: 10.1073/pnas.0506580102 – ident: e_1_3_4_40_2 doi: 10.1038/s41467-020-20654-7 – ident: e_1_3_4_23_2 doi: 10.1186/s12934-021-01583-6 – ident: e_1_3_4_55_2 doi: 10.1038/s41586-021-03594-0 – ident: e_1_3_4_12_2 doi: 10.1016/j.cell.2020.02.058 – ident: e_1_3_4_65_2 doi: 10.1128/mBio.00122-20 – ident: e_1_3_4_29_2 doi: 10.1101/gr.849004 – ident: e_1_3_4_41_2 doi: 10.1016/j.cbpa.2015.10.002 – ident: e_1_3_4_11_2 doi: 10.1021/acsnano.0c08379 – ident: e_1_3_4_16_2 doi: 10.1038/s41586-020-2599-8 – ident: e_1_3_4_44_2 doi: 10.1001/jama.2021.1114 – ident: e_1_3_4_18_2 doi: 10.1080/21645515.2021.1901545 – ident: e_1_3_4_58_2 doi: 10.1038/nmeth.4197 – ident: e_1_3_4_17_2 doi: 10.1080/21645515.2020.1740560 – ident: e_1_3_4_50_2 doi: 10.1016/j.cell.2021.06.020 – ident: e_1_3_4_1_2 doi: 10.1056/NEJMp2003762 – ident: e_1_3_4_22_2 doi: 10.1002/bit.27724 – ident: e_1_3_4_7_2 doi: 10.1056/NEJMoa1501184 – ident: e_1_3_4_49_2 doi: 10.1016/j.xcrm.2021.100255 – ident: e_1_3_4_4_2 doi: 10.1056/NEJMoa2034577 – ident: e_1_3_4_6_2 doi: 10.1016/j.vaccine.2020.10.064 – ident: e_1_3_4_47_2 doi: 10.1016/j.chom.2020.11.007 – ident: e_1_3_4_26_2 doi: 10.1007/s00253-015-6470-z – ident: e_1_3_4_31_2 doi: 10.1002/prot.25594 – ident: e_1_3_4_27_2 doi: 10.1038/s41586-020-2179-y – ident: e_1_3_4_51_2 doi: 10.1126/science.abg8985 – ident: e_1_3_4_35_2 doi: 10.1038/s41586-020-2607-z – ident: e_1_3_4_60_2 doi: 10.1093/bioinformatics/btp616 – ident: e_1_3_4_25_2 doi: 10.1016/j.xphs.2017.04.037 – ident: e_1_3_4_68_2 doi: 10.1126/science.abc4776 – ident: e_1_3_4_8_2 doi: 10.1080/21645515.2017.1289301 – ident: e_1_3_4_61_2 doi: 10.1093/nar/gks042 – ident: e_1_3_4_67_2 doi: 10.1126/science.abc6284 – ident: e_1_3_4_24_2 doi: 10.1080/22221751.2020.1729069 – ident: e_1_3_4_66_2 doi: 10.1038/nature02463 – ident: e_1_3_4_64_2 doi: 10.1038/s41541-020-0187-4 – ident: e_1_3_4_36_2 doi: 10.1155/2019/6491738 – ident: e_1_3_4_19_2 doi: 10.1016/j.virol.2009.07.018 – ident: e_1_3_4_53_2 doi: 10.1056/NEJMoa2103055 – ident: e_1_3_4_32_2 doi: 10.1002/btpr.2966 – ident: e_1_3_4_38_2 doi: 10.1038/s41591-021-01318-5 – ident: e_1_3_4_46_2 doi: 10.1101/2021.01.04.425316 – ident: e_1_3_4_13_2 doi: 10.1038/ncomms8712 – ident: e_1_3_4_39_2 doi: 10.1016/j.cell.2020.10.043 – ident: e_1_3_4_2_2 doi: 10.1038/d41586-020-03134-2 – ident: e_1_3_4_30_2 doi: 10.1016/j.jmb.2005.11.035 – ident: e_1_3_4_42_2 doi: 10.1016/j.vaccine.2017.05.054 – reference: 33688647 - bioRxiv. 2021 Mar 04:2021.03.03.433558. doi: 10.1101/2021.03.03.433558 |
| SSID | ssj0009580 |
| Score | 2.5836403 |
| Snippet | Global containment of COVID-19 still requires accessible and affordable vaccines for low- and middle-income countries (LMICs). Recently approved vaccines... Most of the global population resides in low- and middle-income countries, where current vaccines for COVID-19 remain largely unavailable. For the COVID-19... |
| SourceID | pubmedcentral proquest pubmed crossref jstor |
| SourceType | Open Access Repository Aggregation Database Index Database Enrichment Source Publisher |
| StartPage | 1 |
| SubjectTerms | 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 coronavirus 2 Spike Glycoprotein, Coronavirus - genetics Vaccines Vaccines, Subunit Viral diseases Virus-like particles Weight loss Weight reduction Yeast |
| Title | Engineered SARS-CoV-2 receptor binding domain improves manufacturability in yeast and immunogenicity in mice |
| URI | https://www.jstor.org/stable/27075636 https://www.ncbi.nlm.nih.gov/pubmed/34493582 https://www.proquest.com/docview/2576366529 https://www.proquest.com/docview/2570373476 https://pubmed.ncbi.nlm.nih.gov/PMC8463846 |
| Volume | 118 |
| hasFullText | 1 |
| inHoldings | 1 |
| isFullTextHit | |
| isPrint | |
| link | http://utb.summon.serialssolutions.com/2.0.0/link/0/eLvHCXMwnV3fb9MwELbKeOEFMWBQGMhIPAxVLk2cH_VjNTYqNMo0MtS3yEncLVKbVG2CxP4M_mLuEjtptyINHhpVceJUua_nu_Pdd4S8lxas6gM5YC5oYIaM4CyyHJdJf6ZmiYi4N8AC568Tb3zpfJm6007n90bWUllE_fhmZ13J_0gVzoFcsUr2HyTbTAon4DvIF44gYTjeS8aGTBCNxtHFd3ac_2B2D3SYWhaYhZnWJStJvgD_HwsiVzmSzC5kVmJBQ7mqSbqr0r9f2MSn3krAkpEcHprGemyhE-SMFXverHprk2MwMUHFUVuiovXGusd655O24fEnOf9Z74pgBLoN017kySq9KtUNGy2RM6sKzKrVVZq3AdcxvAWTx41xjQLTFZr4dZCjrZvrVtxn6Vrq2gsd1rAtzMGoa6W1JgZDhnlO3Uu0r3acM-q71d-loYq5sy6AIsNmxplc98HH9YbIyjZsl0Cz7T_5Fp5enp2Fwck0eEAe2uB6YFeMz1Nrg8h5WDNc6J9i6KJ8_vHW9FuWTp3susuNuZ2Nu2HeBE_IY-2X0FENsn3SUdlTsm8kSI80PfmHZ2Teoo62qKMGdVSjjtaoowZ19A7qKIxWqKOAOrqNOhxD1D0nwelJcDxmumcHi8H0LJjyh8LBJhsJuG4yGcxEoiwVOzM1UNJ2EpcrcJgtd-bE3IPVxYuE44sINIWQMrL5AdnL8ky9JBQMa08lfgSrjMTNXeELS6gkslxf2LGIu6RvXm8Yaz57bKsyD6u8Cp-HKI-wlUeXHDU3LGsql79felDJq7nO9sG09rjXJYdGgKFWBHAf-Ozc81xbdMm7ZhjUNO69yUzlZXXNgPvc8WGKF7W8m8m542A2gt0l_hYSmguQAn57JEuvKyp48B44fF7d47mvyaP2f3ZI9opVqd6AQV1EbyuE_wEO1M-Q |
| linkProvider | Geneva Foundation for Medical Education and Research |
| openUrl | ctx_ver=Z39.88-2004&ctx_enc=info%3Aofi%2Fenc%3AUTF-8&rfr_id=info%3Asid%2Fsummon.serialssolutions.com&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=Engineered+SARS-CoV-2+receptor+binding+domain+improves+manufacturability+in+yeast+and+immunogenicity+in+mice&rft.jtitle=Proceedings+of+the+National+Academy+of+Sciences+-+PNAS&rft.au=Dalvie%2C+Neil+C&rft.au=Rodriguez-Aponte%2C+Sergio+A&rft.au=Hartwell%2C+Brittany+L&rft.au=Tostanoski%2C+Lisa+H&rft.date=2021-09-21&rft.issn=1091-6490&rft.eissn=1091-6490&rft.volume=118&rft.issue=38&rft_id=info:doi/10.1073%2Fpnas.2106845118&rft.externalDBID=NO_FULL_TEXT |
| thumbnail_l | http://covers-cdn.summon.serialssolutions.com/index.aspx?isbn=/lc.gif&issn=0027-8424&client=summon |
| thumbnail_m | http://covers-cdn.summon.serialssolutions.com/index.aspx?isbn=/mc.gif&issn=0027-8424&client=summon |
| thumbnail_s | http://covers-cdn.summon.serialssolutions.com/index.aspx?isbn=/sc.gif&issn=0027-8424&client=summon |