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A Novel Targeted RIG-I Receptor 5′Triphosphate Double Strain RNA-Based Adjuvant Significantly Improves the Immunogenicity of the SARS-CoV-2 Delta-Omicron Chimeric RBD-Dimer Recombinant Protein Vaccine

The rapid mutation and spread of SARS-CoV-2 variants recently, especially through the emerging variants Omicron BA5, BF7, XBB and BQ1, necessitate the development of universal vaccines to provide broad spectrum protection against variants. For the SARS-CoV-2 universal recombinant protein vaccines, a...

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Autores principales: Bai, Yu, An, Chaoqiang, Zhang, Xuanxuan, Li, Kelei, Cheng, Feiran, Cui, Bopei, Song, Ziyang, Liu, Dong, Zhang, Jialu, He, Qian, Liu, Jianyang, Mao, Qunying, Liang, Zhenglun
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10220529/
https://www.ncbi.nlm.nih.gov/pubmed/37243185
http://dx.doi.org/10.3390/v15051099
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author Bai, Yu
An, Chaoqiang
Zhang, Xuanxuan
Li, Kelei
Cheng, Feiran
Cui, Bopei
Song, Ziyang
Liu, Dong
Zhang, Jialu
He, Qian
Liu, Jianyang
Mao, Qunying
Liang, Zhenglun
author_facet Bai, Yu
An, Chaoqiang
Zhang, Xuanxuan
Li, Kelei
Cheng, Feiran
Cui, Bopei
Song, Ziyang
Liu, Dong
Zhang, Jialu
He, Qian
Liu, Jianyang
Mao, Qunying
Liang, Zhenglun
author_sort Bai, Yu
collection PubMed
description The rapid mutation and spread of SARS-CoV-2 variants recently, especially through the emerging variants Omicron BA5, BF7, XBB and BQ1, necessitate the development of universal vaccines to provide broad spectrum protection against variants. For the SARS-CoV-2 universal recombinant protein vaccines, an effective approach is necessary to design broad-spectrum antigens and combine them with novel adjuvants that can induce high immunogenicity. In this study, we designed a novel targeted retinoic acid-inducible gene-I (RIG-I) receptor 5′triphosphate double strain RNA (5′PPP dsRNA)-based vaccine adjuvant (named AT149) and combined it with the SARS-CoV-2 Delta and Omicron chimeric RBD-dimer recombinant protein (D-O RBD) to immunize mice. The results showed that AT149 activated the P65 NF-κB signaling pathway, which subsequently activated the interferon signal pathway by targeting the RIG-I receptor. The D-O RBD + AT149 and D-O RBD + aluminum hydroxide adjuvant (Al) + AT149 groups showed elevated levels of neutralizing antibodies against the authentic Delta variant, and Omicron subvariants, BA1, BA5, and BF7, pseudovirus BQ1.1, and XBB compared with D-O RBD + Al and D-O RBD + Al + CpG7909/Poly (I:C) groups at 14 d after the second immunization, respectively. In addition, D-O RBD + AT149 and D-O RBD + Al + AT149 groups presented higher levels of the T-cell-secreted IFN-γ immune response. Overall, we designed a novel targeted RIG-I receptor 5′PPP dsRNA-based vaccine adjuvant to significantly improve the immunogenicity and broad spectrum of the SARS-CoV-2 recombinant protein vaccine.
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spelling pubmed-102205292023-05-28 A Novel Targeted RIG-I Receptor 5′Triphosphate Double Strain RNA-Based Adjuvant Significantly Improves the Immunogenicity of the SARS-CoV-2 Delta-Omicron Chimeric RBD-Dimer Recombinant Protein Vaccine Bai, Yu An, Chaoqiang Zhang, Xuanxuan Li, Kelei Cheng, Feiran Cui, Bopei Song, Ziyang Liu, Dong Zhang, Jialu He, Qian Liu, Jianyang Mao, Qunying Liang, Zhenglun Viruses Brief Report The rapid mutation and spread of SARS-CoV-2 variants recently, especially through the emerging variants Omicron BA5, BF7, XBB and BQ1, necessitate the development of universal vaccines to provide broad spectrum protection against variants. For the SARS-CoV-2 universal recombinant protein vaccines, an effective approach is necessary to design broad-spectrum antigens and combine them with novel adjuvants that can induce high immunogenicity. In this study, we designed a novel targeted retinoic acid-inducible gene-I (RIG-I) receptor 5′triphosphate double strain RNA (5′PPP dsRNA)-based vaccine adjuvant (named AT149) and combined it with the SARS-CoV-2 Delta and Omicron chimeric RBD-dimer recombinant protein (D-O RBD) to immunize mice. The results showed that AT149 activated the P65 NF-κB signaling pathway, which subsequently activated the interferon signal pathway by targeting the RIG-I receptor. The D-O RBD + AT149 and D-O RBD + aluminum hydroxide adjuvant (Al) + AT149 groups showed elevated levels of neutralizing antibodies against the authentic Delta variant, and Omicron subvariants, BA1, BA5, and BF7, pseudovirus BQ1.1, and XBB compared with D-O RBD + Al and D-O RBD + Al + CpG7909/Poly (I:C) groups at 14 d after the second immunization, respectively. In addition, D-O RBD + AT149 and D-O RBD + Al + AT149 groups presented higher levels of the T-cell-secreted IFN-γ immune response. Overall, we designed a novel targeted RIG-I receptor 5′PPP dsRNA-based vaccine adjuvant to significantly improve the immunogenicity and broad spectrum of the SARS-CoV-2 recombinant protein vaccine. MDPI 2023-04-29 /pmc/articles/PMC10220529/ /pubmed/37243185 http://dx.doi.org/10.3390/v15051099 Text en © 2023 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 Brief Report
Bai, Yu
An, Chaoqiang
Zhang, Xuanxuan
Li, Kelei
Cheng, Feiran
Cui, Bopei
Song, Ziyang
Liu, Dong
Zhang, Jialu
He, Qian
Liu, Jianyang
Mao, Qunying
Liang, Zhenglun
A Novel Targeted RIG-I Receptor 5′Triphosphate Double Strain RNA-Based Adjuvant Significantly Improves the Immunogenicity of the SARS-CoV-2 Delta-Omicron Chimeric RBD-Dimer Recombinant Protein Vaccine
title A Novel Targeted RIG-I Receptor 5′Triphosphate Double Strain RNA-Based Adjuvant Significantly Improves the Immunogenicity of the SARS-CoV-2 Delta-Omicron Chimeric RBD-Dimer Recombinant Protein Vaccine
title_full A Novel Targeted RIG-I Receptor 5′Triphosphate Double Strain RNA-Based Adjuvant Significantly Improves the Immunogenicity of the SARS-CoV-2 Delta-Omicron Chimeric RBD-Dimer Recombinant Protein Vaccine
title_fullStr A Novel Targeted RIG-I Receptor 5′Triphosphate Double Strain RNA-Based Adjuvant Significantly Improves the Immunogenicity of the SARS-CoV-2 Delta-Omicron Chimeric RBD-Dimer Recombinant Protein Vaccine
title_full_unstemmed A Novel Targeted RIG-I Receptor 5′Triphosphate Double Strain RNA-Based Adjuvant Significantly Improves the Immunogenicity of the SARS-CoV-2 Delta-Omicron Chimeric RBD-Dimer Recombinant Protein Vaccine
title_short A Novel Targeted RIG-I Receptor 5′Triphosphate Double Strain RNA-Based Adjuvant Significantly Improves the Immunogenicity of the SARS-CoV-2 Delta-Omicron Chimeric RBD-Dimer Recombinant Protein Vaccine
title_sort novel targeted rig-i receptor 5′triphosphate double strain rna-based adjuvant significantly improves the immunogenicity of the sars-cov-2 delta-omicron chimeric rbd-dimer recombinant protein vaccine
topic Brief Report
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10220529/
https://www.ncbi.nlm.nih.gov/pubmed/37243185
http://dx.doi.org/10.3390/v15051099
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