RBD conjugate vaccine with a built-in TLR1/2 agonist is highly immunogenic against SARS-CoV-2 and variants of concern
The coronavirus 2019 (COVID-19) pandemic is causing serious impacts in the world, and safe and effective vaccines and medicines are the best methods to combat the disease. The receptor-binding domain (RBD) of the SARS-CoV-2 spike protein plays a key role in interacting with the angiotensin-convertin...
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creator | Zhou, Shi-Hao Zhang, Ru-Yan Zhang, Hai-Wei Liu, Yan-Ling Wen, Yu Wang, Jian Li, Yu-Ting You, Zi-Wei Yin, Xu-Guang Qiu, Hong Gong, Rui Yang, Guang-Fu Guo, Jun |
description | The coronavirus 2019 (COVID-19) pandemic is causing serious impacts in the world, and safe and effective vaccines and medicines are the best methods to combat the disease. The receptor-binding domain (RBD) of the SARS-CoV-2 spike protein plays a key role in interacting with the angiotensin-converting enzyme 2 (ACE2) receptor, and is regarded as an important target of vaccines. Herein, we constructed the adjuvant-protein conjugate Pam
3
CSK
4
-RBD as a vaccine candidate, in which the
N
-terminal of the RBD was site-selectively oxidized by transamination and conjugated with the TLR1/2 agonist Pam
3
CSK
4
. This demonstrated that the conjugation of Pam
3
CSK
4
significantly enhanced the anti-RBD antibody response and cellular response. In addition, sera from the Pam
3
CSK
4
-RBD immunized group efficiently inhibited the binding of the RBD to ACE2 and protected cells from SARS-CoV-2 and four variants of concern (alpha, beta, gamma and delta), indicating that this adjuvant strategy could be one of the effective means for protein vaccine development.
An RBD-based subunit vaccine with a built-in TLR1/2 agonist induced potent immune responses against SARS-CoV-2 and variants of concern. |
doi_str_mv | 10.1039/d1cc06520c |
format | Article |
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3
CSK
4
-RBD as a vaccine candidate, in which the
N
-terminal of the RBD was site-selectively oxidized by transamination and conjugated with the TLR1/2 agonist Pam
3
CSK
4
. This demonstrated that the conjugation of Pam
3
CSK
4
significantly enhanced the anti-RBD antibody response and cellular response. In addition, sera from the Pam
3
CSK
4
-RBD immunized group efficiently inhibited the binding of the RBD to ACE2 and protected cells from SARS-CoV-2 and four variants of concern (alpha, beta, gamma and delta), indicating that this adjuvant strategy could be one of the effective means for protein vaccine development.
An RBD-based subunit vaccine with a built-in TLR1/2 agonist induced potent immune responses against SARS-CoV-2 and variants of concern.</description><identifier>ISSN: 1359-7345</identifier><identifier>EISSN: 1364-548X</identifier><identifier>DOI: 10.1039/d1cc06520c</identifier><identifier>PMID: 35040862</identifier><language>eng</language><publisher>England: Royal Society of Chemistry</publisher><subject>Angiotensin-Converting Enzyme 2 - metabolism ; Animals ; Antibodies ; Antibody Formation ; Antigens, CD - metabolism ; Antigens, Differentiation, Myelomonocytic - metabolism ; Binding ; Conjugates ; Conjugation ; Coronaviruses ; COVID-19 ; COVID-19 - prevention & control ; COVID-19 - virology ; Female ; HEK293 Cells ; Humans ; Immunization ; Lipopeptides - chemistry ; Macrophages - cytology ; Macrophages - immunology ; Macrophages - metabolism ; Mice ; Mice, Inbred BALB C ; Protein Binding ; Protein Domains - immunology ; Proteins ; RAW 264.7 Cells ; Receptors ; Recombinant Proteins - biosynthesis ; Recombinant Proteins - immunology ; SARS-CoV-2 - immunology ; SARS-CoV-2 - isolation & purification ; SARS-CoV-2 - metabolism ; Severe acute respiratory syndrome coronavirus 2 ; Spike Glycoprotein, Coronavirus - chemistry ; Spike Glycoprotein, Coronavirus - genetics ; Spike Glycoprotein, Coronavirus - immunology ; Spike Glycoprotein, Coronavirus - metabolism ; Vaccines ; Vaccines, Conjugate - administration & dosage ; Vaccines, Conjugate - chemistry ; Vaccines, Conjugate - immunology ; Viral diseases</subject><ispartof>Chemical communications (Cambridge, England), 2022-02, Vol.58 (13), p.212-2123</ispartof><rights>Copyright Royal Society of Chemistry 2022</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c378t-772c855feaf4e153eb705ff9bcdb64d72f028f719df19d52fa63ad116faacadc3</citedby><cites>FETCH-LOGICAL-c378t-772c855feaf4e153eb705ff9bcdb64d72f028f719df19d52fa63ad116faacadc3</cites><orcidid>0000-0002-2097-5054</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,776,780,27901,27902</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/35040862$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Zhou, Shi-Hao</creatorcontrib><creatorcontrib>Zhang, Ru-Yan</creatorcontrib><creatorcontrib>Zhang, Hai-Wei</creatorcontrib><creatorcontrib>Liu, Yan-Ling</creatorcontrib><creatorcontrib>Wen, Yu</creatorcontrib><creatorcontrib>Wang, Jian</creatorcontrib><creatorcontrib>Li, Yu-Ting</creatorcontrib><creatorcontrib>You, Zi-Wei</creatorcontrib><creatorcontrib>Yin, Xu-Guang</creatorcontrib><creatorcontrib>Qiu, Hong</creatorcontrib><creatorcontrib>Gong, Rui</creatorcontrib><creatorcontrib>Yang, Guang-Fu</creatorcontrib><creatorcontrib>Guo, Jun</creatorcontrib><title>RBD conjugate vaccine with a built-in TLR1/2 agonist is highly immunogenic against SARS-CoV-2 and variants of concern</title><title>Chemical communications (Cambridge, England)</title><addtitle>Chem Commun (Camb)</addtitle><description>The coronavirus 2019 (COVID-19) pandemic is causing serious impacts in the world, and safe and effective vaccines and medicines are the best methods to combat the disease. The receptor-binding domain (RBD) of the SARS-CoV-2 spike protein plays a key role in interacting with the angiotensin-converting enzyme 2 (ACE2) receptor, and is regarded as an important target of vaccines. Herein, we constructed the adjuvant-protein conjugate Pam
3
CSK
4
-RBD as a vaccine candidate, in which the
N
-terminal of the RBD was site-selectively oxidized by transamination and conjugated with the TLR1/2 agonist Pam
3
CSK
4
. This demonstrated that the conjugation of Pam
3
CSK
4
significantly enhanced the anti-RBD antibody response and cellular response. In addition, sera from the Pam
3
CSK
4
-RBD immunized group efficiently inhibited the binding of the RBD to ACE2 and protected cells from SARS-CoV-2 and four variants of concern (alpha, beta, gamma and delta), indicating that this adjuvant strategy could be one of the effective means for protein vaccine development.
An RBD-based subunit vaccine with a built-in TLR1/2 agonist induced potent immune responses against SARS-CoV-2 and variants of concern.</description><subject>Angiotensin-Converting Enzyme 2 - metabolism</subject><subject>Animals</subject><subject>Antibodies</subject><subject>Antibody Formation</subject><subject>Antigens, CD - metabolism</subject><subject>Antigens, Differentiation, Myelomonocytic - metabolism</subject><subject>Binding</subject><subject>Conjugates</subject><subject>Conjugation</subject><subject>Coronaviruses</subject><subject>COVID-19</subject><subject>COVID-19 - prevention & control</subject><subject>COVID-19 - virology</subject><subject>Female</subject><subject>HEK293 Cells</subject><subject>Humans</subject><subject>Immunization</subject><subject>Lipopeptides - chemistry</subject><subject>Macrophages - cytology</subject><subject>Macrophages - immunology</subject><subject>Macrophages - metabolism</subject><subject>Mice</subject><subject>Mice, Inbred BALB C</subject><subject>Protein Binding</subject><subject>Protein Domains - immunology</subject><subject>Proteins</subject><subject>RAW 264.7 Cells</subject><subject>Receptors</subject><subject>Recombinant Proteins - biosynthesis</subject><subject>Recombinant Proteins - immunology</subject><subject>SARS-CoV-2 - immunology</subject><subject>SARS-CoV-2 - isolation & purification</subject><subject>SARS-CoV-2 - metabolism</subject><subject>Severe acute respiratory syndrome coronavirus 2</subject><subject>Spike Glycoprotein, Coronavirus - chemistry</subject><subject>Spike Glycoprotein, Coronavirus - genetics</subject><subject>Spike Glycoprotein, Coronavirus - immunology</subject><subject>Spike Glycoprotein, Coronavirus - metabolism</subject><subject>Vaccines</subject><subject>Vaccines, Conjugate - administration & dosage</subject><subject>Vaccines, Conjugate - chemistry</subject><subject>Vaccines, Conjugate - immunology</subject><subject>Viral diseases</subject><issn>1359-7345</issn><issn>1364-548X</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2022</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpdkdtLBCEUxiWK7i-9F0IvEUx5GXX2saYrLATbhd4Gx9FdlxktnSn673PbLpCgHvh-5_PgB8AeRicY0dFpg5VCnBGkVsAmpjzPWF48ry5qNsoEzdkG2IpxjtLCrFgHG5ShHBWcbIJhcn4BlXfzYSp7Dd-kUtZp-G77GZSwHmzbZ9bBh_EEnxIop97Z2EMb4cxOZ-0HtF03OD_VzqqkSuuSen82uc9K_5SlBtckz2Cl6yP0ZvGS0sHtgDUj26h3v-9t8Hh1-VDeZOO769vybJwpKoo-E4KogjGjpck1ZlTXAjFjRrVqap43ghhECiPwqDFpM2Ikp7LBmBsplWwU3QZHS9-X4F8HHfuqs1HptpVO-yFWhBOMSDpFQg__oXM_BJemW1ACi4ILnqjjJaWCjzFoU70E28nwUWFULcKoLnBZfoVRJvjg23KoO938oj-_n4D9JRCi-lX_0qSfbs6NnA</recordid><startdate>20220210</startdate><enddate>20220210</enddate><creator>Zhou, Shi-Hao</creator><creator>Zhang, Ru-Yan</creator><creator>Zhang, Hai-Wei</creator><creator>Liu, Yan-Ling</creator><creator>Wen, Yu</creator><creator>Wang, Jian</creator><creator>Li, Yu-Ting</creator><creator>You, Zi-Wei</creator><creator>Yin, Xu-Guang</creator><creator>Qiu, Hong</creator><creator>Gong, Rui</creator><creator>Yang, Guang-Fu</creator><creator>Guo, Jun</creator><general>Royal Society of Chemistry</general><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>7SR</scope><scope>7U5</scope><scope>8BQ</scope><scope>8FD</scope><scope>JG9</scope><scope>L7M</scope><scope>7X8</scope><orcidid>https://orcid.org/0000-0002-2097-5054</orcidid></search><sort><creationdate>20220210</creationdate><title>RBD conjugate vaccine with a built-in TLR1/2 agonist is highly immunogenic against SARS-CoV-2 and variants of concern</title><author>Zhou, Shi-Hao ; Zhang, Ru-Yan ; Zhang, Hai-Wei ; Liu, Yan-Ling ; Wen, Yu ; Wang, Jian ; Li, Yu-Ting ; You, Zi-Wei ; Yin, Xu-Guang ; Qiu, Hong ; Gong, Rui ; Yang, Guang-Fu ; Guo, Jun</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c378t-772c855feaf4e153eb705ff9bcdb64d72f028f719df19d52fa63ad116faacadc3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2022</creationdate><topic>Angiotensin-Converting Enzyme 2 - metabolism</topic><topic>Animals</topic><topic>Antibodies</topic><topic>Antibody Formation</topic><topic>Antigens, CD - metabolism</topic><topic>Antigens, Differentiation, Myelomonocytic - metabolism</topic><topic>Binding</topic><topic>Conjugates</topic><topic>Conjugation</topic><topic>Coronaviruses</topic><topic>COVID-19</topic><topic>COVID-19 - prevention & control</topic><topic>COVID-19 - virology</topic><topic>Female</topic><topic>HEK293 Cells</topic><topic>Humans</topic><topic>Immunization</topic><topic>Lipopeptides - chemistry</topic><topic>Macrophages - cytology</topic><topic>Macrophages - immunology</topic><topic>Macrophages - metabolism</topic><topic>Mice</topic><topic>Mice, Inbred BALB C</topic><topic>Protein Binding</topic><topic>Protein Domains - immunology</topic><topic>Proteins</topic><topic>RAW 264.7 Cells</topic><topic>Receptors</topic><topic>Recombinant Proteins - biosynthesis</topic><topic>Recombinant Proteins - immunology</topic><topic>SARS-CoV-2 - immunology</topic><topic>SARS-CoV-2 - isolation & purification</topic><topic>SARS-CoV-2 - metabolism</topic><topic>Severe acute respiratory syndrome coronavirus 2</topic><topic>Spike Glycoprotein, Coronavirus - chemistry</topic><topic>Spike Glycoprotein, Coronavirus - genetics</topic><topic>Spike Glycoprotein, Coronavirus - immunology</topic><topic>Spike Glycoprotein, Coronavirus - metabolism</topic><topic>Vaccines</topic><topic>Vaccines, Conjugate - administration & dosage</topic><topic>Vaccines, Conjugate - chemistry</topic><topic>Vaccines, Conjugate - immunology</topic><topic>Viral diseases</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Zhou, Shi-Hao</creatorcontrib><creatorcontrib>Zhang, Ru-Yan</creatorcontrib><creatorcontrib>Zhang, Hai-Wei</creatorcontrib><creatorcontrib>Liu, Yan-Ling</creatorcontrib><creatorcontrib>Wen, Yu</creatorcontrib><creatorcontrib>Wang, Jian</creatorcontrib><creatorcontrib>Li, Yu-Ting</creatorcontrib><creatorcontrib>You, Zi-Wei</creatorcontrib><creatorcontrib>Yin, Xu-Guang</creatorcontrib><creatorcontrib>Qiu, Hong</creatorcontrib><creatorcontrib>Gong, Rui</creatorcontrib><creatorcontrib>Yang, Guang-Fu</creatorcontrib><creatorcontrib>Guo, Jun</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Engineered Materials Abstracts</collection><collection>Solid State and Superconductivity Abstracts</collection><collection>METADEX</collection><collection>Technology Research Database</collection><collection>Materials Research Database</collection><collection>Advanced Technologies Database with Aerospace</collection><collection>MEDLINE - Academic</collection><jtitle>Chemical communications (Cambridge, England)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Zhou, Shi-Hao</au><au>Zhang, Ru-Yan</au><au>Zhang, Hai-Wei</au><au>Liu, Yan-Ling</au><au>Wen, Yu</au><au>Wang, Jian</au><au>Li, Yu-Ting</au><au>You, Zi-Wei</au><au>Yin, Xu-Guang</au><au>Qiu, Hong</au><au>Gong, Rui</au><au>Yang, Guang-Fu</au><au>Guo, Jun</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>RBD conjugate vaccine with a built-in TLR1/2 agonist is highly immunogenic against SARS-CoV-2 and variants of concern</atitle><jtitle>Chemical communications (Cambridge, England)</jtitle><addtitle>Chem Commun (Camb)</addtitle><date>2022-02-10</date><risdate>2022</risdate><volume>58</volume><issue>13</issue><spage>212</spage><epage>2123</epage><pages>212-2123</pages><issn>1359-7345</issn><eissn>1364-548X</eissn><abstract>The coronavirus 2019 (COVID-19) pandemic is causing serious impacts in the world, and safe and effective vaccines and medicines are the best methods to combat the disease. The receptor-binding domain (RBD) of the SARS-CoV-2 spike protein plays a key role in interacting with the angiotensin-converting enzyme 2 (ACE2) receptor, and is regarded as an important target of vaccines. Herein, we constructed the adjuvant-protein conjugate Pam
3
CSK
4
-RBD as a vaccine candidate, in which the
N
-terminal of the RBD was site-selectively oxidized by transamination and conjugated with the TLR1/2 agonist Pam
3
CSK
4
. This demonstrated that the conjugation of Pam
3
CSK
4
significantly enhanced the anti-RBD antibody response and cellular response. In addition, sera from the Pam
3
CSK
4
-RBD immunized group efficiently inhibited the binding of the RBD to ACE2 and protected cells from SARS-CoV-2 and four variants of concern (alpha, beta, gamma and delta), indicating that this adjuvant strategy could be one of the effective means for protein vaccine development.
An RBD-based subunit vaccine with a built-in TLR1/2 agonist induced potent immune responses against SARS-CoV-2 and variants of concern.</abstract><cop>England</cop><pub>Royal Society of Chemistry</pub><pmid>35040862</pmid><doi>10.1039/d1cc06520c</doi><tpages>4</tpages><orcidid>https://orcid.org/0000-0002-2097-5054</orcidid></addata></record> |
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source | MEDLINE; Royal Society Of Chemistry Journals 2008-; Alma/SFX Local Collection |
subjects | Angiotensin-Converting Enzyme 2 - metabolism Animals Antibodies Antibody Formation Antigens, CD - metabolism Antigens, Differentiation, Myelomonocytic - metabolism Binding Conjugates Conjugation Coronaviruses COVID-19 COVID-19 - prevention & control COVID-19 - virology Female HEK293 Cells Humans Immunization Lipopeptides - chemistry Macrophages - cytology Macrophages - immunology Macrophages - metabolism Mice Mice, Inbred BALB C Protein Binding Protein Domains - immunology Proteins RAW 264.7 Cells Receptors Recombinant Proteins - biosynthesis Recombinant Proteins - immunology SARS-CoV-2 - immunology SARS-CoV-2 - isolation & purification SARS-CoV-2 - metabolism Severe acute respiratory syndrome coronavirus 2 Spike Glycoprotein, Coronavirus - chemistry Spike Glycoprotein, Coronavirus - genetics Spike Glycoprotein, Coronavirus - immunology Spike Glycoprotein, Coronavirus - metabolism Vaccines Vaccines, Conjugate - administration & dosage Vaccines, Conjugate - chemistry Vaccines, Conjugate - immunology Viral diseases |
title | RBD conjugate vaccine with a built-in TLR1/2 agonist is highly immunogenic against SARS-CoV-2 and variants of concern |
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