Elicitation of Potent Neutralizing Antibody Responses by Designed Protein Nanoparticle Vaccines for SARS-CoV-2
A safe, effective, and scalable vaccine is needed to halt the ongoing SARS-CoV-2 pandemic. We describe the structure-based design of self-assembling protein nanoparticle immunogens that elicit potent and protective antibody responses against SARS-CoV-2 in mice. The nanoparticle vaccines display 60 S...
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creator | Walls, Alexandra C. Fiala, Brooke Schäfer, Alexandra Wrenn, Samuel Pham, Minh N. Murphy, Michael Tse, Longping V. Shehata, Laila O’Connor, Megan A. Chen, Chengbo Navarro, Mary Jane Miranda, Marcos C. Pettie, Deleah Ravichandran, Rashmi Kraft, John C. Ogohara, Cassandra Palser, Anne Chalk, Sara Lee, E-Chiang Guerriero, Kathryn Kepl, Elizabeth Chow, Cameron M. Sydeman, Claire Hodge, Edgar A. Brown, Brieann Fuller, Jim T. Dinnon, Kenneth H. Gralinski, Lisa E. Leist, Sarah R. Gully, Kendra L. Lewis, Thomas B. Guttman, Miklos Chu, Helen Y. Lee, Kelly K. Fuller, Deborah H. Baric, Ralph S. Kellam, Paul Carter, Lauren Pepper, Marion Sheahan, Timothy P. Veesler, David King, Neil P. |
description | A safe, effective, and scalable vaccine is needed to halt the ongoing SARS-CoV-2 pandemic. We describe the structure-based design of self-assembling protein nanoparticle immunogens that elicit potent and protective antibody responses against SARS-CoV-2 in mice. The nanoparticle vaccines display 60 SARS-CoV-2 spike receptor-binding domains (RBDs) in a highly immunogenic array and induce neutralizing antibody titers 10-fold higher than the prefusion-stabilized spike despite a 5-fold lower dose. Antibodies elicited by the RBD nanoparticles target multiple distinct epitopes, suggesting they may not be easily susceptible to escape mutations, and exhibit a lower binding:neutralizing ratio than convalescent human sera, which may minimize the risk of vaccine-associated enhanced respiratory disease. The high yield and stability of the assembled nanoparticles suggest that manufacture of the nanoparticle vaccines will be highly scalable. These results highlight the utility of robust antigen display platforms and have launched cGMP manufacturing efforts to advance the SARS-CoV-2-RBD nanoparticle vaccine into the clinic.
[Display omitted]
•Two-component nanoparticle platform enabled rapid generation of SARS-CoV-2 vaccines•The RBD-nanoparticle vaccines elicit potent neutralizing antibody responses•Nanoparticle vaccine-elicited antibodies target multiple non-overlapping epitopes•The lead nanoparticle vaccine candidate is being manufactured for clinical trials
Walls et al. describe a potential nanoparticle vaccine for COVID-19, made of a self-assembling protein nanoparticle displaying the SARS-CoV-2 receptor-binding domain in a highly immunogenic array reminiscent of the natural virus. Their nanoparticle vaccine candidate elicits a diverse, potent, and protective antibody response, including neutralizing antibody titers 10-fold higher than the prefusion-stabilized spike ectodomain trimer. |
doi_str_mv | 10.1016/j.cell.2020.10.043 |
format | Article |
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[Display omitted]
•Two-component nanoparticle platform enabled rapid generation of SARS-CoV-2 vaccines•The RBD-nanoparticle vaccines elicit potent neutralizing antibody responses•Nanoparticle vaccine-elicited antibodies target multiple non-overlapping epitopes•The lead nanoparticle vaccine candidate is being manufactured for clinical trials
Walls et al. describe a potential nanoparticle vaccine for COVID-19, made of a self-assembling protein nanoparticle displaying the SARS-CoV-2 receptor-binding domain in a highly immunogenic array reminiscent of the natural virus. Their nanoparticle vaccine candidate elicits a diverse, potent, and protective antibody response, including neutralizing antibody titers 10-fold higher than the prefusion-stabilized spike ectodomain trimer.</description><identifier>ISSN: 0092-8674</identifier><identifier>EISSN: 1097-4172</identifier><identifier>DOI: 10.1016/j.cell.2020.10.043</identifier><identifier>PMID: 33160446</identifier><language>eng</language><publisher>United States: Elsevier Inc</publisher><subject>Adolescent ; Adult ; Aged ; Animals ; Antibodies, Neutralizing - immunology ; Antibodies, Viral - immunology ; Chlorocebus aethiops ; Cohort Studies ; computational protein design ; COVID-19 - prevention & control ; COVID-19 - virology ; COVID-19 Vaccines - immunology ; Epitopes - immunology ; Female ; HEK293 Cells ; Humans ; Macaca nemestrina ; Male ; Mice, Inbred BALB C ; Middle Aged ; nanoparticle ; Nanoparticles - chemistry ; protein ; Protein Domains - immunology ; RBD ; SARS-CoV-2 ; SARS-CoV-2 - genetics ; SARS-CoV-2 - immunology ; Spike Glycoprotein, Coronavirus - chemistry ; Spike Glycoprotein, Coronavirus - immunology ; Vaccination ; vaccine ; Vero Cells ; Young Adult</subject><ispartof>Cell, 2020-11, Vol.183 (5), p.1367-1382.e17</ispartof><rights>2020 The Authors</rights><rights>Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.</rights><rights>2020 The Authors 2020</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><cites>FETCH-LOGICAL-c500t-ab0cb5fd4a95f90e6ab1d31a18b62aadbbdf4529e3090ef9466757bd5e22188c3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1016/j.cell.2020.10.043$$EHTML$$P50$$Gelsevier$$Hfree_for_read</linktohtml><link.rule.ids>230,315,781,785,886,3551,27926,27927,45997</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/33160446$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Walls, Alexandra C.</creatorcontrib><creatorcontrib>Fiala, Brooke</creatorcontrib><creatorcontrib>Schäfer, Alexandra</creatorcontrib><creatorcontrib>Wrenn, Samuel</creatorcontrib><creatorcontrib>Pham, Minh N.</creatorcontrib><creatorcontrib>Murphy, Michael</creatorcontrib><creatorcontrib>Tse, Longping V.</creatorcontrib><creatorcontrib>Shehata, Laila</creatorcontrib><creatorcontrib>O’Connor, Megan A.</creatorcontrib><creatorcontrib>Chen, Chengbo</creatorcontrib><creatorcontrib>Navarro, Mary Jane</creatorcontrib><creatorcontrib>Miranda, Marcos C.</creatorcontrib><creatorcontrib>Pettie, Deleah</creatorcontrib><creatorcontrib>Ravichandran, Rashmi</creatorcontrib><creatorcontrib>Kraft, John C.</creatorcontrib><creatorcontrib>Ogohara, Cassandra</creatorcontrib><creatorcontrib>Palser, Anne</creatorcontrib><creatorcontrib>Chalk, Sara</creatorcontrib><creatorcontrib>Lee, E-Chiang</creatorcontrib><creatorcontrib>Guerriero, Kathryn</creatorcontrib><creatorcontrib>Kepl, Elizabeth</creatorcontrib><creatorcontrib>Chow, Cameron M.</creatorcontrib><creatorcontrib>Sydeman, Claire</creatorcontrib><creatorcontrib>Hodge, Edgar A.</creatorcontrib><creatorcontrib>Brown, Brieann</creatorcontrib><creatorcontrib>Fuller, Jim T.</creatorcontrib><creatorcontrib>Dinnon, Kenneth H.</creatorcontrib><creatorcontrib>Gralinski, Lisa E.</creatorcontrib><creatorcontrib>Leist, Sarah R.</creatorcontrib><creatorcontrib>Gully, Kendra L.</creatorcontrib><creatorcontrib>Lewis, Thomas B.</creatorcontrib><creatorcontrib>Guttman, Miklos</creatorcontrib><creatorcontrib>Chu, Helen Y.</creatorcontrib><creatorcontrib>Lee, Kelly K.</creatorcontrib><creatorcontrib>Fuller, Deborah H.</creatorcontrib><creatorcontrib>Baric, Ralph S.</creatorcontrib><creatorcontrib>Kellam, Paul</creatorcontrib><creatorcontrib>Carter, Lauren</creatorcontrib><creatorcontrib>Pepper, Marion</creatorcontrib><creatorcontrib>Sheahan, Timothy P.</creatorcontrib><creatorcontrib>Veesler, David</creatorcontrib><creatorcontrib>King, Neil P.</creatorcontrib><title>Elicitation of Potent Neutralizing Antibody Responses by Designed Protein Nanoparticle Vaccines for SARS-CoV-2</title><title>Cell</title><addtitle>Cell</addtitle><description>A safe, effective, and scalable vaccine is needed to halt the ongoing SARS-CoV-2 pandemic. We describe the structure-based design of self-assembling protein nanoparticle immunogens that elicit potent and protective antibody responses against SARS-CoV-2 in mice. The nanoparticle vaccines display 60 SARS-CoV-2 spike receptor-binding domains (RBDs) in a highly immunogenic array and induce neutralizing antibody titers 10-fold higher than the prefusion-stabilized spike despite a 5-fold lower dose. Antibodies elicited by the RBD nanoparticles target multiple distinct epitopes, suggesting they may not be easily susceptible to escape mutations, and exhibit a lower binding:neutralizing ratio than convalescent human sera, which may minimize the risk of vaccine-associated enhanced respiratory disease. The high yield and stability of the assembled nanoparticles suggest that manufacture of the nanoparticle vaccines will be highly scalable. These results highlight the utility of robust antigen display platforms and have launched cGMP manufacturing efforts to advance the SARS-CoV-2-RBD nanoparticle vaccine into the clinic.
[Display omitted]
•Two-component nanoparticle platform enabled rapid generation of SARS-CoV-2 vaccines•The RBD-nanoparticle vaccines elicit potent neutralizing antibody responses•Nanoparticle vaccine-elicited antibodies target multiple non-overlapping epitopes•The lead nanoparticle vaccine candidate is being manufactured for clinical trials
Walls et al. describe a potential nanoparticle vaccine for COVID-19, made of a self-assembling protein nanoparticle displaying the SARS-CoV-2 receptor-binding domain in a highly immunogenic array reminiscent of the natural virus. Their nanoparticle vaccine candidate elicits a diverse, potent, and protective antibody response, including neutralizing antibody titers 10-fold higher than the prefusion-stabilized spike ectodomain trimer.</description><subject>Adolescent</subject><subject>Adult</subject><subject>Aged</subject><subject>Animals</subject><subject>Antibodies, Neutralizing - immunology</subject><subject>Antibodies, Viral - immunology</subject><subject>Chlorocebus aethiops</subject><subject>Cohort Studies</subject><subject>computational protein design</subject><subject>COVID-19 - prevention & control</subject><subject>COVID-19 - virology</subject><subject>COVID-19 Vaccines - immunology</subject><subject>Epitopes - immunology</subject><subject>Female</subject><subject>HEK293 Cells</subject><subject>Humans</subject><subject>Macaca nemestrina</subject><subject>Male</subject><subject>Mice, Inbred BALB C</subject><subject>Middle Aged</subject><subject>nanoparticle</subject><subject>Nanoparticles - chemistry</subject><subject>protein</subject><subject>Protein Domains - immunology</subject><subject>RBD</subject><subject>SARS-CoV-2</subject><subject>SARS-CoV-2 - genetics</subject><subject>SARS-CoV-2 - immunology</subject><subject>Spike Glycoprotein, Coronavirus - chemistry</subject><subject>Spike Glycoprotein, Coronavirus - immunology</subject><subject>Vaccination</subject><subject>vaccine</subject><subject>Vero Cells</subject><subject>Young 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S.</creator><creator>Kellam, Paul</creator><creator>Carter, Lauren</creator><creator>Pepper, Marion</creator><creator>Sheahan, Timothy P.</creator><creator>Veesler, David</creator><creator>King, Neil P.</creator><general>Elsevier Inc</general><general>Cell Press</general><scope>6I.</scope><scope>AAFTH</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>5PM</scope></search><sort><creationdate>20201125</creationdate><title>Elicitation of Potent Neutralizing Antibody Responses by Designed Protein Nanoparticle Vaccines for SARS-CoV-2</title><author>Walls, Alexandra C. ; Fiala, Brooke ; Schäfer, Alexandra ; Wrenn, Samuel ; Pham, Minh N. ; Murphy, Michael ; Tse, Longping V. ; Shehata, Laila ; O’Connor, Megan A. ; Chen, Chengbo ; Navarro, Mary Jane ; Miranda, Marcos C. ; Pettie, Deleah ; Ravichandran, Rashmi ; Kraft, John C. ; Ogohara, Cassandra ; Palser, Anne ; Chalk, Sara ; Lee, E-Chiang ; Guerriero, Kathryn ; Kepl, Elizabeth ; Chow, Cameron M. ; Sydeman, Claire ; Hodge, Edgar A. ; Brown, Brieann ; Fuller, Jim T. ; Dinnon, Kenneth H. ; Gralinski, Lisa E. ; Leist, Sarah R. ; Gully, Kendra L. ; Lewis, Thomas B. ; Guttman, Miklos ; Chu, Helen Y. ; Lee, Kelly K. ; Fuller, Deborah H. ; Baric, Ralph S. ; Kellam, Paul ; Carter, Lauren ; Pepper, Marion ; Sheahan, Timothy P. ; Veesler, David ; King, Neil P.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c500t-ab0cb5fd4a95f90e6ab1d31a18b62aadbbdf4529e3090ef9466757bd5e22188c3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2020</creationdate><topic>Adolescent</topic><topic>Adult</topic><topic>Aged</topic><topic>Animals</topic><topic>Antibodies, Neutralizing - immunology</topic><topic>Antibodies, Viral - immunology</topic><topic>Chlorocebus aethiops</topic><topic>Cohort Studies</topic><topic>computational protein 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P.</creatorcontrib><collection>ScienceDirect Open Access Titles</collection><collection>Elsevier:ScienceDirect:Open Access</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Cell</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Walls, Alexandra C.</au><au>Fiala, Brooke</au><au>Schäfer, Alexandra</au><au>Wrenn, Samuel</au><au>Pham, Minh N.</au><au>Murphy, Michael</au><au>Tse, Longping V.</au><au>Shehata, Laila</au><au>O’Connor, Megan A.</au><au>Chen, Chengbo</au><au>Navarro, Mary Jane</au><au>Miranda, Marcos C.</au><au>Pettie, Deleah</au><au>Ravichandran, Rashmi</au><au>Kraft, John C.</au><au>Ogohara, Cassandra</au><au>Palser, Anne</au><au>Chalk, Sara</au><au>Lee, E-Chiang</au><au>Guerriero, Kathryn</au><au>Kepl, Elizabeth</au><au>Chow, Cameron M.</au><au>Sydeman, Claire</au><au>Hodge, Edgar A.</au><au>Brown, Brieann</au><au>Fuller, Jim T.</au><au>Dinnon, Kenneth H.</au><au>Gralinski, Lisa E.</au><au>Leist, Sarah R.</au><au>Gully, Kendra L.</au><au>Lewis, Thomas B.</au><au>Guttman, Miklos</au><au>Chu, Helen Y.</au><au>Lee, Kelly K.</au><au>Fuller, Deborah H.</au><au>Baric, Ralph S.</au><au>Kellam, Paul</au><au>Carter, Lauren</au><au>Pepper, Marion</au><au>Sheahan, Timothy P.</au><au>Veesler, David</au><au>King, Neil P.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Elicitation of Potent Neutralizing Antibody Responses by Designed Protein Nanoparticle Vaccines for SARS-CoV-2</atitle><jtitle>Cell</jtitle><addtitle>Cell</addtitle><date>2020-11-25</date><risdate>2020</risdate><volume>183</volume><issue>5</issue><spage>1367</spage><epage>1382.e17</epage><pages>1367-1382.e17</pages><issn>0092-8674</issn><eissn>1097-4172</eissn><abstract>A safe, effective, and scalable vaccine is needed to halt the ongoing SARS-CoV-2 pandemic. We describe the structure-based design of self-assembling protein nanoparticle immunogens that elicit potent and protective antibody responses against SARS-CoV-2 in mice. The nanoparticle vaccines display 60 SARS-CoV-2 spike receptor-binding domains (RBDs) in a highly immunogenic array and induce neutralizing antibody titers 10-fold higher than the prefusion-stabilized spike despite a 5-fold lower dose. Antibodies elicited by the RBD nanoparticles target multiple distinct epitopes, suggesting they may not be easily susceptible to escape mutations, and exhibit a lower binding:neutralizing ratio than convalescent human sera, which may minimize the risk of vaccine-associated enhanced respiratory disease. The high yield and stability of the assembled nanoparticles suggest that manufacture of the nanoparticle vaccines will be highly scalable. These results highlight the utility of robust antigen display platforms and have launched cGMP manufacturing efforts to advance the SARS-CoV-2-RBD nanoparticle vaccine into the clinic.
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•Two-component nanoparticle platform enabled rapid generation of SARS-CoV-2 vaccines•The RBD-nanoparticle vaccines elicit potent neutralizing antibody responses•Nanoparticle vaccine-elicited antibodies target multiple non-overlapping epitopes•The lead nanoparticle vaccine candidate is being manufactured for clinical trials
Walls et al. describe a potential nanoparticle vaccine for COVID-19, made of a self-assembling protein nanoparticle displaying the SARS-CoV-2 receptor-binding domain in a highly immunogenic array reminiscent of the natural virus. Their nanoparticle vaccine candidate elicits a diverse, potent, and protective antibody response, including neutralizing antibody titers 10-fold higher than the prefusion-stabilized spike ectodomain trimer.</abstract><cop>United States</cop><pub>Elsevier Inc</pub><pmid>33160446</pmid><doi>10.1016/j.cell.2020.10.043</doi><oa>free_for_read</oa></addata></record> |
fulltext | fulltext |
identifier | ISSN: 0092-8674 |
ispartof | Cell, 2020-11, Vol.183 (5), p.1367-1382.e17 |
issn | 0092-8674 1097-4172 |
language | eng |
recordid | cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_7604136 |
source | MEDLINE; Access via ScienceDirect (Elsevier); EZB Electronic Journals Library; Cell Press Free Archives(OpenAccess) |
subjects | Adolescent Adult Aged Animals Antibodies, Neutralizing - immunology Antibodies, Viral - immunology Chlorocebus aethiops Cohort Studies computational protein design COVID-19 - prevention & control COVID-19 - virology COVID-19 Vaccines - immunology Epitopes - immunology Female HEK293 Cells Humans Macaca nemestrina Male Mice, Inbred BALB C Middle Aged nanoparticle Nanoparticles - chemistry protein Protein Domains - immunology RBD SARS-CoV-2 SARS-CoV-2 - genetics SARS-CoV-2 - immunology Spike Glycoprotein, Coronavirus - chemistry Spike Glycoprotein, Coronavirus - immunology Vaccination vaccine Vero Cells Young Adult |
title | Elicitation of Potent Neutralizing Antibody Responses by Designed Protein Nanoparticle Vaccines for SARS-CoV-2 |
url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2024-12-17T23%3A22%3A25IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-elsevier_pubme&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Elicitation%20of%20Potent%20Neutralizing%20Antibody%20Responses%20by%20Designed%20Protein%20Nanoparticle%20Vaccines%20for%20SARS-CoV-2&rft.jtitle=Cell&rft.au=Walls,%20Alexandra%20C.&rft.date=2020-11-25&rft.volume=183&rft.issue=5&rft.spage=1367&rft.epage=1382.e17&rft.pages=1367-1382.e17&rft.issn=0092-8674&rft.eissn=1097-4172&rft_id=info:doi/10.1016/j.cell.2020.10.043&rft_dat=%3Celsevier_pubme%3ES0092867420314501%3C/elsevier_pubme%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_id=info:pmid/33160446&rft_els_id=S0092867420314501&rfr_iscdi=true |