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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Veröffentlicht in:Chemical communications (Cambridge, England) England), 2022-02, Vol.58 (13), p.212-2123
Hauptverfasser: 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
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container_issue 13
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container_title Chemical communications (Cambridge, England)
container_volume 58
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
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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. 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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. 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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 &amp; 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 &amp; 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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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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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