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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MDPI AG
2023-04-01
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| Series: | Viruses |
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| Online Access: | https://www.mdpi.com/1999-4915/15/5/1099 |
| _version_ | 1797598118096666624 |
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| author | Yu Bai Chaoqiang An Xuanxuan Zhang Kelei Li Feiran Cheng Bopei Cui Ziyang Song Dong Liu Jialu Zhang Qian He Jianyang Liu Qunying Mao Zhenglun Liang |
| author_facet | Yu Bai Chaoqiang An Xuanxuan Zhang Kelei Li Feiran Cheng Bopei Cui Ziyang Song Dong Liu Jialu Zhang Qian He Jianyang Liu Qunying Mao Zhenglun Liang |
| author_sort | Yu Bai |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-03-11T03:14:48Z |
| format | Article |
| id | doaj.art-d3600b1a943a49968f4240b6c499fc8e |
| institution | Directory Open Access Journal |
| issn | 1999-4915 |
| language | English |
| last_indexed | 2024-03-11T03:14:48Z |
| publishDate | 2023-04-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Viruses |
| spelling | doaj.art-d3600b1a943a49968f4240b6c499fc8e2023-11-18T03:38:59ZengMDPI AGViruses1999-49152023-04-01155109910.3390/v15051099A 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 VaccineYu Bai0Chaoqiang An1Xuanxuan Zhang2Kelei Li3Feiran Cheng4Bopei Cui5Ziyang Song6Dong Liu7Jialu Zhang8Qian He9Jianyang Liu10Qunying Mao11Zhenglun Liang12Division of Hepatitis and Enterovirus Vaccines, Institute of Biological Products, National Institutes for Food and Drug Control, NHC Key Laboratory of Research on Quality and Standardization of Biotech Products, NMPA Key Laboratory for Quality Research and Evaluation of Biological Products, Beijing 102600, ChinaShanghai JunTuo Biotechnology Co., Ltd., Shanghai 201210, ChinaDivision of Hepatitis and Enterovirus Vaccines, Institute of Biological Products, National Institutes for Food and Drug Control, NHC Key Laboratory of Research on Quality and Standardization of Biotech Products, NMPA Key Laboratory for Quality Research and Evaluation of Biological Products, Beijing 102600, ChinaBeijing Minhai Biotechnology Co., Ltd., Beijning 102600, ChinaDivision of Hepatitis and Enterovirus Vaccines, Institute of Biological Products, National Institutes for Food and Drug Control, NHC Key Laboratory of Research on Quality and Standardization of Biotech Products, NMPA Key Laboratory for Quality Research and Evaluation of Biological Products, Beijing 102600, ChinaDivision of Hepatitis and Enterovirus Vaccines, Institute of Biological Products, National Institutes for Food and Drug Control, NHC Key Laboratory of Research on Quality and Standardization of Biotech Products, NMPA Key Laboratory for Quality Research and Evaluation of Biological Products, Beijing 102600, ChinaDivision of Hepatitis and Enterovirus Vaccines, Institute of Biological Products, National Institutes for Food and Drug Control, NHC Key Laboratory of Research on Quality and Standardization of Biotech Products, NMPA Key Laboratory for Quality Research and Evaluation of Biological Products, Beijing 102600, ChinaDivision of Hepatitis and Enterovirus Vaccines, Institute of Biological Products, National Institutes for Food and Drug Control, NHC Key Laboratory of Research on Quality and Standardization of Biotech Products, NMPA Key Laboratory for Quality Research and Evaluation of Biological Products, Beijing 102600, ChinaDivision of Hepatitis and Enterovirus Vaccines, Institute of Biological Products, National Institutes for Food and Drug Control, NHC Key Laboratory of Research on Quality and Standardization of Biotech Products, NMPA Key Laboratory for Quality Research and Evaluation of Biological Products, Beijing 102600, ChinaDivision of Hepatitis and Enterovirus Vaccines, Institute of Biological Products, National Institutes for Food and Drug Control, NHC Key Laboratory of Research on Quality and Standardization of Biotech Products, NMPA Key Laboratory for Quality Research and Evaluation of Biological Products, Beijing 102600, ChinaDivision of Hepatitis and Enterovirus Vaccines, Institute of Biological Products, National Institutes for Food and Drug Control, NHC Key Laboratory of Research on Quality and Standardization of Biotech Products, NMPA Key Laboratory for Quality Research and Evaluation of Biological Products, Beijing 102600, ChinaDivision of Hepatitis and Enterovirus Vaccines, Institute of Biological Products, National Institutes for Food and Drug Control, NHC Key Laboratory of Research on Quality and Standardization of Biotech Products, NMPA Key Laboratory for Quality Research and Evaluation of Biological Products, Beijing 102600, ChinaDivision of Hepatitis and Enterovirus Vaccines, Institute of Biological Products, National Institutes for Food and Drug Control, NHC Key Laboratory of Research on Quality and Standardization of Biotech Products, NMPA Key Laboratory for Quality Research and Evaluation of Biological Products, Beijing 102600, ChinaThe 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.https://www.mdpi.com/1999-4915/15/5/1099retinoic acid-inducible gene-I (RIG-I) receptorvaccine adjuvantimmunogenicityrecombinant protein vaccine |
| spellingShingle | Yu Bai Chaoqiang An Xuanxuan Zhang Kelei Li Feiran Cheng Bopei Cui Ziyang Song Dong Liu Jialu Zhang Qian He Jianyang Liu Qunying Mao Zhenglun Liang 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 Viruses retinoic acid-inducible gene-I (RIG-I) receptor vaccine adjuvant immunogenicity 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 | retinoic acid-inducible gene-I (RIG-I) receptor vaccine adjuvant immunogenicity recombinant protein vaccine |
| url | https://www.mdpi.com/1999-4915/15/5/1099 |
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