Human Fc-Conjugated Receptor Binding Domain-Based Recombinant Subunit Vaccines with Short Linker Induce Potent Neutralizing Antibodies against Multiple SARS-CoV-2 Variants

The coronavirus disease-19 (COVID-19) pandemic has been ongoing since December 2019, with more than 6.3 million deaths reported globally as of August 2022. Despite the success of several SARS-CoV-2 vaccines, the rise in variants, some of which are resistant to the effects of vaccination, highlights...

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Autores principales: Chen, Liqing, Qi, Xiaoxiao, Liang, Dan, Li, Guiqi, Peng, Xiaofang, Li, Xiaohui, Ke, Bixia, Zheng, Huanying, Liu, Zhongqiu, Ke, Changwen, Liao, Guochao, Liu, Liang, Feng, Qian
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9505662/
https://www.ncbi.nlm.nih.gov/pubmed/36146579
http://dx.doi.org/10.3390/vaccines10091502
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author Chen, Liqing
Qi, Xiaoxiao
Liang, Dan
Li, Guiqi
Peng, Xiaofang
Li, Xiaohui
Ke, Bixia
Zheng, Huanying
Liu, Zhongqiu
Ke, Changwen
Liao, Guochao
Liu, Liang
Feng, Qian
author_facet Chen, Liqing
Qi, Xiaoxiao
Liang, Dan
Li, Guiqi
Peng, Xiaofang
Li, Xiaohui
Ke, Bixia
Zheng, Huanying
Liu, Zhongqiu
Ke, Changwen
Liao, Guochao
Liu, Liang
Feng, Qian
author_sort Chen, Liqing
collection PubMed
description The coronavirus disease-19 (COVID-19) pandemic has been ongoing since December 2019, with more than 6.3 million deaths reported globally as of August 2022. Despite the success of several SARS-CoV-2 vaccines, the rise in variants, some of which are resistant to the effects of vaccination, highlights the need for a so-called pan-coronavirus (universal) vaccine. Here, we performed an immunogenicity comparison of prototype vaccines containing spike protein receptor-binding domain (RBD) residues 319–541, or spike protein regions S1, S2 and S fused to a histidine-tagged or human IgG1 Fc (hFC) fragment with either a longer (six residues) or shorter (three residues) linker. While all recombinant protein vaccines developed were effective in eliciting humoral immunity, the RBD-hFc vaccine was able to generate a potent neutralizing antibody response as well as a cellular immune response. We then compared the effects of recombinant protein length and linker size on immunogenicity in vivo. We found that a longer recombinant RBD protein (residues 319–583; RBD-Plus-hFc) containing a small alanine linker (AAA) was able to trigger long-lasting, high-titer neutralizing antibodies in mice. Finally, we evaluated cross-neutralization of wild-type and mutant RBD-Plus-hFc vaccines against wild-type, Alpha, Beta, Delta and Omicron SARS-CoV-2 variants. Significantly, at the same antigen dose, wild-type RBD-Plus-hFc immune sera induced broadly neutralizing antibodies against wild-type, Alpha, Beta, Delta and Omicron variants. Taken together, our findings provide valuable information for the continued development of recombinant protein-based SARS-CoV-2 vaccines and a basic foundation for booster vaccinations to avoid reinfection with SARS-CoV-2 variants.
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spelling pubmed-95056622022-09-24 Human Fc-Conjugated Receptor Binding Domain-Based Recombinant Subunit Vaccines with Short Linker Induce Potent Neutralizing Antibodies against Multiple SARS-CoV-2 Variants Chen, Liqing Qi, Xiaoxiao Liang, Dan Li, Guiqi Peng, Xiaofang Li, Xiaohui Ke, Bixia Zheng, Huanying Liu, Zhongqiu Ke, Changwen Liao, Guochao Liu, Liang Feng, Qian Vaccines (Basel) Article The coronavirus disease-19 (COVID-19) pandemic has been ongoing since December 2019, with more than 6.3 million deaths reported globally as of August 2022. Despite the success of several SARS-CoV-2 vaccines, the rise in variants, some of which are resistant to the effects of vaccination, highlights the need for a so-called pan-coronavirus (universal) vaccine. Here, we performed an immunogenicity comparison of prototype vaccines containing spike protein receptor-binding domain (RBD) residues 319–541, or spike protein regions S1, S2 and S fused to a histidine-tagged or human IgG1 Fc (hFC) fragment with either a longer (six residues) or shorter (three residues) linker. While all recombinant protein vaccines developed were effective in eliciting humoral immunity, the RBD-hFc vaccine was able to generate a potent neutralizing antibody response as well as a cellular immune response. We then compared the effects of recombinant protein length and linker size on immunogenicity in vivo. We found that a longer recombinant RBD protein (residues 319–583; RBD-Plus-hFc) containing a small alanine linker (AAA) was able to trigger long-lasting, high-titer neutralizing antibodies in mice. Finally, we evaluated cross-neutralization of wild-type and mutant RBD-Plus-hFc vaccines against wild-type, Alpha, Beta, Delta and Omicron SARS-CoV-2 variants. Significantly, at the same antigen dose, wild-type RBD-Plus-hFc immune sera induced broadly neutralizing antibodies against wild-type, Alpha, Beta, Delta and Omicron variants. Taken together, our findings provide valuable information for the continued development of recombinant protein-based SARS-CoV-2 vaccines and a basic foundation for booster vaccinations to avoid reinfection with SARS-CoV-2 variants. MDPI 2022-09-08 /pmc/articles/PMC9505662/ /pubmed/36146579 http://dx.doi.org/10.3390/vaccines10091502 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Chen, Liqing
Qi, Xiaoxiao
Liang, Dan
Li, Guiqi
Peng, Xiaofang
Li, Xiaohui
Ke, Bixia
Zheng, Huanying
Liu, Zhongqiu
Ke, Changwen
Liao, Guochao
Liu, Liang
Feng, Qian
Human Fc-Conjugated Receptor Binding Domain-Based Recombinant Subunit Vaccines with Short Linker Induce Potent Neutralizing Antibodies against Multiple SARS-CoV-2 Variants
title Human Fc-Conjugated Receptor Binding Domain-Based Recombinant Subunit Vaccines with Short Linker Induce Potent Neutralizing Antibodies against Multiple SARS-CoV-2 Variants
title_full Human Fc-Conjugated Receptor Binding Domain-Based Recombinant Subunit Vaccines with Short Linker Induce Potent Neutralizing Antibodies against Multiple SARS-CoV-2 Variants
title_fullStr Human Fc-Conjugated Receptor Binding Domain-Based Recombinant Subunit Vaccines with Short Linker Induce Potent Neutralizing Antibodies against Multiple SARS-CoV-2 Variants
title_full_unstemmed Human Fc-Conjugated Receptor Binding Domain-Based Recombinant Subunit Vaccines with Short Linker Induce Potent Neutralizing Antibodies against Multiple SARS-CoV-2 Variants
title_short Human Fc-Conjugated Receptor Binding Domain-Based Recombinant Subunit Vaccines with Short Linker Induce Potent Neutralizing Antibodies against Multiple SARS-CoV-2 Variants
title_sort human fc-conjugated receptor binding domain-based recombinant subunit vaccines with short linker induce potent neutralizing antibodies against multiple sars-cov-2 variants
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9505662/
https://www.ncbi.nlm.nih.gov/pubmed/36146579
http://dx.doi.org/10.3390/vaccines10091502
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