Loading…
Computationally designed Spike antigens induce neutralising responses against the breadth of SARS-COV-2 variants
Updates of SARS-CoV-2 vaccines are required to generate immunity in the population against constantly evolving SARS-CoV-2 variants of concerns (VOCs). Here we describe three novel in-silico designed spike-based antigens capable of inducing neutralising antibodies across a spectrum of SARS-CoV-2 VOCs...
Saved in:
Published in: | npj vaccines 2024-09, Vol.9 (1), p.164-9, Article 164 |
---|---|
Main Authors: | , , , , , , , , , , , , , , , , , , , , , , , , , |
Format: | Article |
Language: | English |
Subjects: | |
Citations: | Items that this one cites |
Online Access: | Get full text |
Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
cited_by | |
---|---|
cites | cdi_FETCH-LOGICAL-c378t-52e670aa4b2ab6ffa23ac9d5845184c3d39260099cc800ac505ae4fe858cf1543 |
container_end_page | 9 |
container_issue | 1 |
container_start_page | 164 |
container_title | npj vaccines |
container_volume | 9 |
creator | Vishwanath, Sneha Carnell, George William Billmeier, Martina Ohlendorf, Luis Neckermann, Patrick Asbach, Benedikt George, Charlotte Sans, Maria Suau Chan, Andrew Olivier, Joey Nadesalingam, Angalee Einhauser, Sebastian Temperton, Nigel Cantoni, Diego Grove, Joe Jordan, Ingo Sandig, Volker Tonks, Paul Geiger, Johannes Dohmen, Christian Mummert, Verena Samuel, Anne Rosalind Plank, Christian Kinsley, Rebecca Wagner, Ralf Heeney, Jonathan Luke |
description | Updates of SARS-CoV-2 vaccines are required to generate immunity in the population against constantly evolving SARS-CoV-2 variants of concerns (VOCs). Here we describe three novel in-silico designed spike-based antigens capable of inducing neutralising antibodies across a spectrum of SARS-CoV-2 VOCs. Three sets of antigens utilising pre-Delta (T2_32), and post-Gamma sequence data (T2_35 and T2_36) were designed. T2_32 elicited superior neutralising responses against VOCs compared to the Wuhan-1 spike antigen in DNA prime-boost immunisation regime in guinea pigs. Heterologous boosting with the attenuated poxvirus - Modified vaccinia Ankara expressing T2_32 induced broader neutralising immune responses in all primed animals. T2_32, T2_35 and T2_36 elicited broader neutralising capacity compared to the Omicron BA.1 spike antigen administered by mRNA immunisation in mice. These findings demonstrate the utility of structure-informed computationally derived modifications of spike-based antigens for inducing broad immune responses covering more than 2 years of evolved SARS-CoV-2 variants. |
doi_str_mv | 10.1038/s41541-024-00950-9 |
format | article |
fullrecord | <record><control><sourceid>proquest_doaj_</sourceid><recordid>TN_cdi_doaj_primary_oai_doaj_org_article_82ef274560d34dc98c35687c198efcf5</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><doaj_id>oai_doaj_org_article_82ef274560d34dc98c35687c198efcf5</doaj_id><sourcerecordid>3102219524</sourcerecordid><originalsourceid>FETCH-LOGICAL-c378t-52e670aa4b2ab6ffa23ac9d5845184c3d39260099cc800ac505ae4fe858cf1543</originalsourceid><addsrcrecordid>eNp9kk9v1DAQxSMEolXpF-CALHHhkuI_cWKfULUqUKlSJRa4WrPOJOslawc7qdRvj7dpS8uBky3P889-M68o3jJ6xqhQH1PFZMVKyquSUi1pqV8Ux5xKXVJG5csn-6PiNKUdpZQ1tZANfV0cCc0lq6k6LsZV2I_zBJMLHobhlrSYXO-xJevR_UICfnI9-kScb2eLxOM8RRhccr4nEdMYfMJEoAfn00SmLZJNRGinLQkdWZ9_W5er658lJzcQXYalN8WrDoaEp_frSfHj88X31dfy6vrL5er8qrSiUVMpOdYNBag2HDZ11wEXYHUrVSWZqqxos4U6G9fWKkrBSioBqw6VVLbLnREnxeXCbQPszBjdHuKtCeDM3UGIvYE4OTugURw73lSypq2oWquVFbJWjWVaYWc7mVmfFtY4b_bYWvSHHjyDPq94tzV9uDGMCVU1QmfCh3tCDL9nTJPZu2RxGMBjmJMRLA-y1jU7SN__I92FOebhLCrOtOQHe3xR2RhSitg9_oZRcwiIWQJiMtfcBcQc0O-e-ni88hCHLBCLIOWS7zH-ffs_2D8y78a5</addsrcrecordid><sourcetype>Open Website</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>3102219524</pqid></control><display><type>article</type><title>Computationally designed Spike antigens induce neutralising responses against the breadth of SARS-COV-2 variants</title><source>Publicly Available Content Database</source><source>PubMed Central</source><source>Coronavirus Research Database</source><source>Springer Nature - nature.com Journals - Fully Open Access</source><creator>Vishwanath, Sneha ; Carnell, George William ; Billmeier, Martina ; Ohlendorf, Luis ; Neckermann, Patrick ; Asbach, Benedikt ; George, Charlotte ; Sans, Maria Suau ; Chan, Andrew ; Olivier, Joey ; Nadesalingam, Angalee ; Einhauser, Sebastian ; Temperton, Nigel ; Cantoni, Diego ; Grove, Joe ; Jordan, Ingo ; Sandig, Volker ; Tonks, Paul ; Geiger, Johannes ; Dohmen, Christian ; Mummert, Verena ; Samuel, Anne Rosalind ; Plank, Christian ; Kinsley, Rebecca ; Wagner, Ralf ; Heeney, Jonathan Luke</creator><creatorcontrib>Vishwanath, Sneha ; Carnell, George William ; Billmeier, Martina ; Ohlendorf, Luis ; Neckermann, Patrick ; Asbach, Benedikt ; George, Charlotte ; Sans, Maria Suau ; Chan, Andrew ; Olivier, Joey ; Nadesalingam, Angalee ; Einhauser, Sebastian ; Temperton, Nigel ; Cantoni, Diego ; Grove, Joe ; Jordan, Ingo ; Sandig, Volker ; Tonks, Paul ; Geiger, Johannes ; Dohmen, Christian ; Mummert, Verena ; Samuel, Anne Rosalind ; Plank, Christian ; Kinsley, Rebecca ; Wagner, Ralf ; Heeney, Jonathan Luke</creatorcontrib><description>Updates of SARS-CoV-2 vaccines are required to generate immunity in the population against constantly evolving SARS-CoV-2 variants of concerns (VOCs). Here we describe three novel in-silico designed spike-based antigens capable of inducing neutralising antibodies across a spectrum of SARS-CoV-2 VOCs. Three sets of antigens utilising pre-Delta (T2_32), and post-Gamma sequence data (T2_35 and T2_36) were designed. T2_32 elicited superior neutralising responses against VOCs compared to the Wuhan-1 spike antigen in DNA prime-boost immunisation regime in guinea pigs. Heterologous boosting with the attenuated poxvirus - Modified vaccinia Ankara expressing T2_32 induced broader neutralising immune responses in all primed animals. T2_32, T2_35 and T2_36 elicited broader neutralising capacity compared to the Omicron BA.1 spike antigen administered by mRNA immunisation in mice. These findings demonstrate the utility of structure-informed computationally derived modifications of spike-based antigens for inducing broad immune responses covering more than 2 years of evolved SARS-CoV-2 variants.</description><identifier>ISSN: 2059-0105</identifier><identifier>EISSN: 2059-0105</identifier><identifier>DOI: 10.1038/s41541-024-00950-9</identifier><identifier>PMID: 39251608</identifier><language>eng</language><publisher>London: Nature Publishing Group UK</publisher><subject>631/250/590/1991 ; 631/250/590/2293 ; Antibodies ; Antigens ; Biomedical and Life Sciences ; Biomedicine ; COVID-19 ; COVID-19 vaccines ; Design ; Disease transmission ; Immunity (Disease) ; Immunization ; Infectious Diseases ; Medical Microbiology ; Mutation ; Proteins ; Public Health ; Severe acute respiratory syndrome coronavirus 2 ; Vaccine ; Virology</subject><ispartof>npj vaccines, 2024-09, Vol.9 (1), p.164-9, Article 164</ispartof><rights>The Author(s) 2024</rights><rights>2024. The Author(s).</rights><rights>The Author(s) 2024. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>The Author(s) 2024 2024</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><cites>FETCH-LOGICAL-c378t-52e670aa4b2ab6ffa23ac9d5845184c3d39260099cc800ac505ae4fe858cf1543</cites><orcidid>0000-0002-6585-3288 ; 0000-0001-9960-547X ; 0000-0003-2702-1621 ; 0000-0002-7978-3815 ; 0000-0001-8875-0989 ; 0000-0003-2711-7252</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC11384739/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.proquest.com/docview/3102219524?pq-origsite=primo$$EHTML$$P50$$Gproquest$$Hfree_for_read</linktohtml><link.rule.ids>230,314,725,778,782,883,25736,27907,27908,36995,36996,38499,43878,44573,53774,53776</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/39251608$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Vishwanath, Sneha</creatorcontrib><creatorcontrib>Carnell, George William</creatorcontrib><creatorcontrib>Billmeier, Martina</creatorcontrib><creatorcontrib>Ohlendorf, Luis</creatorcontrib><creatorcontrib>Neckermann, Patrick</creatorcontrib><creatorcontrib>Asbach, Benedikt</creatorcontrib><creatorcontrib>George, Charlotte</creatorcontrib><creatorcontrib>Sans, Maria Suau</creatorcontrib><creatorcontrib>Chan, Andrew</creatorcontrib><creatorcontrib>Olivier, Joey</creatorcontrib><creatorcontrib>Nadesalingam, Angalee</creatorcontrib><creatorcontrib>Einhauser, Sebastian</creatorcontrib><creatorcontrib>Temperton, Nigel</creatorcontrib><creatorcontrib>Cantoni, Diego</creatorcontrib><creatorcontrib>Grove, Joe</creatorcontrib><creatorcontrib>Jordan, Ingo</creatorcontrib><creatorcontrib>Sandig, Volker</creatorcontrib><creatorcontrib>Tonks, Paul</creatorcontrib><creatorcontrib>Geiger, Johannes</creatorcontrib><creatorcontrib>Dohmen, Christian</creatorcontrib><creatorcontrib>Mummert, Verena</creatorcontrib><creatorcontrib>Samuel, Anne Rosalind</creatorcontrib><creatorcontrib>Plank, Christian</creatorcontrib><creatorcontrib>Kinsley, Rebecca</creatorcontrib><creatorcontrib>Wagner, Ralf</creatorcontrib><creatorcontrib>Heeney, Jonathan Luke</creatorcontrib><title>Computationally designed Spike antigens induce neutralising responses against the breadth of SARS-COV-2 variants</title><title>npj vaccines</title><addtitle>npj Vaccines</addtitle><addtitle>NPJ Vaccines</addtitle><description>Updates of SARS-CoV-2 vaccines are required to generate immunity in the population against constantly evolving SARS-CoV-2 variants of concerns (VOCs). Here we describe three novel in-silico designed spike-based antigens capable of inducing neutralising antibodies across a spectrum of SARS-CoV-2 VOCs. Three sets of antigens utilising pre-Delta (T2_32), and post-Gamma sequence data (T2_35 and T2_36) were designed. T2_32 elicited superior neutralising responses against VOCs compared to the Wuhan-1 spike antigen in DNA prime-boost immunisation regime in guinea pigs. Heterologous boosting with the attenuated poxvirus - Modified vaccinia Ankara expressing T2_32 induced broader neutralising immune responses in all primed animals. T2_32, T2_35 and T2_36 elicited broader neutralising capacity compared to the Omicron BA.1 spike antigen administered by mRNA immunisation in mice. These findings demonstrate the utility of structure-informed computationally derived modifications of spike-based antigens for inducing broad immune responses covering more than 2 years of evolved SARS-CoV-2 variants.</description><subject>631/250/590/1991</subject><subject>631/250/590/2293</subject><subject>Antibodies</subject><subject>Antigens</subject><subject>Biomedical and Life Sciences</subject><subject>Biomedicine</subject><subject>COVID-19</subject><subject>COVID-19 vaccines</subject><subject>Design</subject><subject>Disease transmission</subject><subject>Immunity (Disease)</subject><subject>Immunization</subject><subject>Infectious Diseases</subject><subject>Medical Microbiology</subject><subject>Mutation</subject><subject>Proteins</subject><subject>Public Health</subject><subject>Severe acute respiratory syndrome coronavirus 2</subject><subject>Vaccine</subject><subject>Virology</subject><issn>2059-0105</issn><issn>2059-0105</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2024</creationdate><recordtype>article</recordtype><sourceid>COVID</sourceid><sourceid>PIMPY</sourceid><sourceid>DOA</sourceid><recordid>eNp9kk9v1DAQxSMEolXpF-CALHHhkuI_cWKfULUqUKlSJRa4WrPOJOslawc7qdRvj7dpS8uBky3P889-M68o3jJ6xqhQH1PFZMVKyquSUi1pqV8Ux5xKXVJG5csn-6PiNKUdpZQ1tZANfV0cCc0lq6k6LsZV2I_zBJMLHobhlrSYXO-xJevR_UICfnI9-kScb2eLxOM8RRhccr4nEdMYfMJEoAfn00SmLZJNRGinLQkdWZ9_W5er658lJzcQXYalN8WrDoaEp_frSfHj88X31dfy6vrL5er8qrSiUVMpOdYNBag2HDZ11wEXYHUrVSWZqqxos4U6G9fWKkrBSioBqw6VVLbLnREnxeXCbQPszBjdHuKtCeDM3UGIvYE4OTugURw73lSypq2oWquVFbJWjWVaYWc7mVmfFtY4b_bYWvSHHjyDPq94tzV9uDGMCVU1QmfCh3tCDL9nTJPZu2RxGMBjmJMRLA-y1jU7SN__I92FOebhLCrOtOQHe3xR2RhSitg9_oZRcwiIWQJiMtfcBcQc0O-e-ni88hCHLBCLIOWS7zH-ffs_2D8y78a5</recordid><startdate>20240909</startdate><enddate>20240909</enddate><creator>Vishwanath, Sneha</creator><creator>Carnell, George William</creator><creator>Billmeier, Martina</creator><creator>Ohlendorf, Luis</creator><creator>Neckermann, Patrick</creator><creator>Asbach, Benedikt</creator><creator>George, Charlotte</creator><creator>Sans, Maria Suau</creator><creator>Chan, Andrew</creator><creator>Olivier, Joey</creator><creator>Nadesalingam, Angalee</creator><creator>Einhauser, Sebastian</creator><creator>Temperton, Nigel</creator><creator>Cantoni, Diego</creator><creator>Grove, Joe</creator><creator>Jordan, Ingo</creator><creator>Sandig, Volker</creator><creator>Tonks, Paul</creator><creator>Geiger, Johannes</creator><creator>Dohmen, Christian</creator><creator>Mummert, Verena</creator><creator>Samuel, Anne Rosalind</creator><creator>Plank, Christian</creator><creator>Kinsley, Rebecca</creator><creator>Wagner, Ralf</creator><creator>Heeney, Jonathan Luke</creator><general>Nature Publishing Group UK</general><general>Nature Publishing Group</general><general>Nature Portfolio</general><scope>C6C</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>3V.</scope><scope>7RV</scope><scope>7X7</scope><scope>7XB</scope><scope>88C</scope><scope>8C1</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AEUYN</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BENPR</scope><scope>CCPQU</scope><scope>COVID</scope><scope>DWQXO</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>K9-</scope><scope>K9.</scope><scope>KB0</scope><scope>M0R</scope><scope>M0S</scope><scope>M0T</scope><scope>NAPCQ</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>7X8</scope><scope>5PM</scope><scope>DOA</scope><orcidid>https://orcid.org/0000-0002-6585-3288</orcidid><orcidid>https://orcid.org/0000-0001-9960-547X</orcidid><orcidid>https://orcid.org/0000-0003-2702-1621</orcidid><orcidid>https://orcid.org/0000-0002-7978-3815</orcidid><orcidid>https://orcid.org/0000-0001-8875-0989</orcidid><orcidid>https://orcid.org/0000-0003-2711-7252</orcidid></search><sort><creationdate>20240909</creationdate><title>Computationally designed Spike antigens induce neutralising responses against the breadth of SARS-COV-2 variants</title><author>Vishwanath, Sneha ; Carnell, George William ; Billmeier, Martina ; Ohlendorf, Luis ; Neckermann, Patrick ; Asbach, Benedikt ; George, Charlotte ; Sans, Maria Suau ; Chan, Andrew ; Olivier, Joey ; Nadesalingam, Angalee ; Einhauser, Sebastian ; Temperton, Nigel ; Cantoni, Diego ; Grove, Joe ; Jordan, Ingo ; Sandig, Volker ; Tonks, Paul ; Geiger, Johannes ; Dohmen, Christian ; Mummert, Verena ; Samuel, Anne Rosalind ; Plank, Christian ; Kinsley, Rebecca ; Wagner, Ralf ; Heeney, Jonathan Luke</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c378t-52e670aa4b2ab6ffa23ac9d5845184c3d39260099cc800ac505ae4fe858cf1543</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2024</creationdate><topic>631/250/590/1991</topic><topic>631/250/590/2293</topic><topic>Antibodies</topic><topic>Antigens</topic><topic>Biomedical and Life Sciences</topic><topic>Biomedicine</topic><topic>COVID-19</topic><topic>COVID-19 vaccines</topic><topic>Design</topic><topic>Disease transmission</topic><topic>Immunity (Disease)</topic><topic>Immunization</topic><topic>Infectious Diseases</topic><topic>Medical Microbiology</topic><topic>Mutation</topic><topic>Proteins</topic><topic>Public Health</topic><topic>Severe acute respiratory syndrome coronavirus 2</topic><topic>Vaccine</topic><topic>Virology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Vishwanath, Sneha</creatorcontrib><creatorcontrib>Carnell, George William</creatorcontrib><creatorcontrib>Billmeier, Martina</creatorcontrib><creatorcontrib>Ohlendorf, Luis</creatorcontrib><creatorcontrib>Neckermann, Patrick</creatorcontrib><creatorcontrib>Asbach, Benedikt</creatorcontrib><creatorcontrib>George, Charlotte</creatorcontrib><creatorcontrib>Sans, Maria Suau</creatorcontrib><creatorcontrib>Chan, Andrew</creatorcontrib><creatorcontrib>Olivier, Joey</creatorcontrib><creatorcontrib>Nadesalingam, Angalee</creatorcontrib><creatorcontrib>Einhauser, Sebastian</creatorcontrib><creatorcontrib>Temperton, Nigel</creatorcontrib><creatorcontrib>Cantoni, Diego</creatorcontrib><creatorcontrib>Grove, Joe</creatorcontrib><creatorcontrib>Jordan, Ingo</creatorcontrib><creatorcontrib>Sandig, Volker</creatorcontrib><creatorcontrib>Tonks, Paul</creatorcontrib><creatorcontrib>Geiger, Johannes</creatorcontrib><creatorcontrib>Dohmen, Christian</creatorcontrib><creatorcontrib>Mummert, Verena</creatorcontrib><creatorcontrib>Samuel, Anne Rosalind</creatorcontrib><creatorcontrib>Plank, Christian</creatorcontrib><creatorcontrib>Kinsley, Rebecca</creatorcontrib><creatorcontrib>Wagner, Ralf</creatorcontrib><creatorcontrib>Heeney, Jonathan Luke</creatorcontrib><collection>SpringerOpen</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Nursing & Allied Health Database</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Healthcare Administration Database (Alumni)</collection><collection>Public Health Database</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>ProQuest Central (Alumni)</collection><collection>ProQuest One Sustainability</collection><collection>ProQuest Central</collection><collection>ProQuest Central Essentials</collection><collection>ProQuest Central</collection><collection>ProQuest One Community College</collection><collection>Coronavirus Research Database</collection><collection>ProQuest Central Korea</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>Consumer Health Database (Alumni Edition)</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Nursing & Allied Health Database (Alumni Edition)</collection><collection>Consumer Health Database</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Healthcare Administration Database</collection><collection>Nursing & Allied Health Premium</collection><collection>Publicly Available Content Database</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><collection>DOAJ Directory of Open Access Journals</collection><jtitle>npj vaccines</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Vishwanath, Sneha</au><au>Carnell, George William</au><au>Billmeier, Martina</au><au>Ohlendorf, Luis</au><au>Neckermann, Patrick</au><au>Asbach, Benedikt</au><au>George, Charlotte</au><au>Sans, Maria Suau</au><au>Chan, Andrew</au><au>Olivier, Joey</au><au>Nadesalingam, Angalee</au><au>Einhauser, Sebastian</au><au>Temperton, Nigel</au><au>Cantoni, Diego</au><au>Grove, Joe</au><au>Jordan, Ingo</au><au>Sandig, Volker</au><au>Tonks, Paul</au><au>Geiger, Johannes</au><au>Dohmen, Christian</au><au>Mummert, Verena</au><au>Samuel, Anne Rosalind</au><au>Plank, Christian</au><au>Kinsley, Rebecca</au><au>Wagner, Ralf</au><au>Heeney, Jonathan Luke</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Computationally designed Spike antigens induce neutralising responses against the breadth of SARS-COV-2 variants</atitle><jtitle>npj vaccines</jtitle><stitle>npj Vaccines</stitle><addtitle>NPJ Vaccines</addtitle><date>2024-09-09</date><risdate>2024</risdate><volume>9</volume><issue>1</issue><spage>164</spage><epage>9</epage><pages>164-9</pages><artnum>164</artnum><issn>2059-0105</issn><eissn>2059-0105</eissn><abstract>Updates of SARS-CoV-2 vaccines are required to generate immunity in the population against constantly evolving SARS-CoV-2 variants of concerns (VOCs). Here we describe three novel in-silico designed spike-based antigens capable of inducing neutralising antibodies across a spectrum of SARS-CoV-2 VOCs. Three sets of antigens utilising pre-Delta (T2_32), and post-Gamma sequence data (T2_35 and T2_36) were designed. T2_32 elicited superior neutralising responses against VOCs compared to the Wuhan-1 spike antigen in DNA prime-boost immunisation regime in guinea pigs. Heterologous boosting with the attenuated poxvirus - Modified vaccinia Ankara expressing T2_32 induced broader neutralising immune responses in all primed animals. T2_32, T2_35 and T2_36 elicited broader neutralising capacity compared to the Omicron BA.1 spike antigen administered by mRNA immunisation in mice. These findings demonstrate the utility of structure-informed computationally derived modifications of spike-based antigens for inducing broad immune responses covering more than 2 years of evolved SARS-CoV-2 variants.</abstract><cop>London</cop><pub>Nature Publishing Group UK</pub><pmid>39251608</pmid><doi>10.1038/s41541-024-00950-9</doi><tpages>9</tpages><orcidid>https://orcid.org/0000-0002-6585-3288</orcidid><orcidid>https://orcid.org/0000-0001-9960-547X</orcidid><orcidid>https://orcid.org/0000-0003-2702-1621</orcidid><orcidid>https://orcid.org/0000-0002-7978-3815</orcidid><orcidid>https://orcid.org/0000-0001-8875-0989</orcidid><orcidid>https://orcid.org/0000-0003-2711-7252</orcidid><oa>free_for_read</oa></addata></record> |
fulltext | fulltext |
identifier | ISSN: 2059-0105 |
ispartof | npj vaccines, 2024-09, Vol.9 (1), p.164-9, Article 164 |
issn | 2059-0105 2059-0105 |
language | eng |
recordid | cdi_doaj_primary_oai_doaj_org_article_82ef274560d34dc98c35687c198efcf5 |
source | Publicly Available Content Database; PubMed Central; Coronavirus Research Database; Springer Nature - nature.com Journals - Fully Open Access |
subjects | 631/250/590/1991 631/250/590/2293 Antibodies Antigens Biomedical and Life Sciences Biomedicine COVID-19 COVID-19 vaccines Design Disease transmission Immunity (Disease) Immunization Infectious Diseases Medical Microbiology Mutation Proteins Public Health Severe acute respiratory syndrome coronavirus 2 Vaccine Virology |
title | Computationally designed Spike antigens induce neutralising responses against the breadth of SARS-COV-2 variants |
url | http://sfxeu10.hosted.exlibrisgroup.com/loughborough?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-16T21%3A15%3A22IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_doaj_&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Computationally%20designed%20Spike%20antigens%20induce%20neutralising%20responses%20against%20the%20breadth%20of%20SARS-COV-2%20variants&rft.jtitle=npj%20vaccines&rft.au=Vishwanath,%20Sneha&rft.date=2024-09-09&rft.volume=9&rft.issue=1&rft.spage=164&rft.epage=9&rft.pages=164-9&rft.artnum=164&rft.issn=2059-0105&rft.eissn=2059-0105&rft_id=info:doi/10.1038/s41541-024-00950-9&rft_dat=%3Cproquest_doaj_%3E3102219524%3C/proquest_doaj_%3E%3Cgrp_id%3Ecdi_FETCH-LOGICAL-c378t-52e670aa4b2ab6ffa23ac9d5845184c3d39260099cc800ac505ae4fe858cf1543%3C/grp_id%3E%3Coa%3E%3C/oa%3E%3Curl%3E%3C/url%3E&rft_id=info:oai/&rft_pqid=3102219524&rft_id=info:pmid/39251608&rfr_iscdi=true |