mRNA vaccines with RBD mutations have broad-spectrum activity against SARS-CoV-2 variants in mice
Abstract The emergence of SARS-CoV-2 variants with defined mutations that enhance pathogenicity or facilitate immune evasion has resulted in a continual decline in the protective efficacy of existing vaccines. Therefore, there is a pressing need for a vaccine capable of combating future variants. In...
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2025-01-01
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| Series: | npj Vaccines |
| Online Access: | https://doi.org/10.1038/s41541-025-01066-4 |
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| author | Xiaoming Liang Yuxia Yuan Junbin Wang Cong Tang Yun Yang Yanan Zhou Hao Yang Qing Huang Wenhai Yu Haixuan Wang Yuhuan Yan Dongdong Lin Yanwen Li Xuena Du Longhai Yuan Wenqi Quan Daoju Wu Shuaiyao Lu |
| author_facet | Xiaoming Liang Yuxia Yuan Junbin Wang Cong Tang Yun Yang Yanan Zhou Hao Yang Qing Huang Wenhai Yu Haixuan Wang Yuhuan Yan Dongdong Lin Yanwen Li Xuena Du Longhai Yuan Wenqi Quan Daoju Wu Shuaiyao Lu |
| author_sort | Xiaoming Liang |
| collection | DOAJ |
| description | Abstract The emergence of SARS-CoV-2 variants with defined mutations that enhance pathogenicity or facilitate immune evasion has resulted in a continual decline in the protective efficacy of existing vaccines. Therefore, there is a pressing need for a vaccine capable of combating future variants. In this study, we designed new mRNA vaccines, BSCoV05 and BSCoV06, and generated point mutations in the receptor-binding domain (RBD) of the original Wuhan strain to increase their broad-spectrum antiviral activity. Additionally, we used the BA.1 RBD as a control. Both vaccines elicited a robust immune response in BALB/c and K18-hACE2 mice, generating high levels of specific binding antibodies against the BA.2 RBD. Moreover, all three vaccines induced neutralizing antibodies against the prototype viral strain and relevant variants, including the Alpha and Beta strains and the Omicron variants BA.1, BA.2, BA.5, XBB.1.5, XBB.1.16, EG.5.1, and EG.5.1.1, with BSCoV06 demonstrating broader neutralizing antibody activity. Both BSCoV05 and BSCoV06 also elicited a cellular immune response. After the challenge, both BSCoV05 and BSCOV06 provided protection against the EG.5.1 strain in both mouse strains. Therefore, these two vaccines merit further evaluation in nonhuman primates, and this vaccine design strategy should be explored for its potential application in combating future SARS-CoV-2 variants, offering valuable insights into broad-spectrum vaccine development. |
| format | Article |
| id | doaj-art-7f80242c45384275b815c75f474591e7 |
| institution | Kabale University |
| issn | 2059-0105 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | npj Vaccines |
| spelling | doaj-art-7f80242c45384275b815c75f474591e72025-01-19T12:09:19ZengNature Portfolionpj Vaccines2059-01052025-01-0110111110.1038/s41541-025-01066-4mRNA vaccines with RBD mutations have broad-spectrum activity against SARS-CoV-2 variants in miceXiaoming Liang0Yuxia Yuan1Junbin Wang2Cong Tang3Yun Yang4Yanan Zhou5Hao Yang6Qing Huang7Wenhai Yu8Haixuan Wang9Yuhuan Yan10Dongdong Lin11Yanwen Li12Xuena Du13Longhai Yuan14Wenqi Quan15Daoju Wu16Shuaiyao Lu17Institute of Medical Biology, Chinese Academy of Medical Sciences and Peking Union Medical collegeInstitute of Medical Biology, Chinese Academy of Medical Sciences and Peking Union Medical collegeInstitute of Medical Biology, Chinese Academy of Medical Sciences and Peking Union Medical collegeInstitute of Medical Biology, Chinese Academy of Medical Sciences and Peking Union Medical collegeInstitute of Medical Biology, Chinese Academy of Medical Sciences and Peking Union Medical collegeInstitute of Medical Biology, Chinese Academy of Medical Sciences and Peking Union Medical collegeInstitute of Medical Biology, Chinese Academy of Medical Sciences and Peking Union Medical collegeInstitute of Medical Biology, Chinese Academy of Medical Sciences and Peking Union Medical collegeInstitute of Medical Biology, Chinese Academy of Medical Sciences and Peking Union Medical collegeInstitute of Medical Biology, Chinese Academy of Medical Sciences and Peking Union Medical collegeInstitute of Medical Biology, Chinese Academy of Medical Sciences and Peking Union Medical collegeInstitute of Medical Biology, Chinese Academy of Medical Sciences and Peking Union Medical collegeInstitute of Medical Biology, Chinese Academy of Medical Sciences and Peking Union Medical collegeInstitute of Medical Biology, Chinese Academy of Medical Sciences and Peking Union Medical collegeInstitute of Medical Biology, Chinese Academy of Medical Sciences and Peking Union Medical collegeInstitute of Medical Biology, Chinese Academy of Medical Sciences and Peking Union Medical collegeInstitute of Medical Biology, Chinese Academy of Medical Sciences and Peking Union Medical collegeInstitute of Medical Biology, Chinese Academy of Medical Sciences and Peking Union Medical collegeAbstract The emergence of SARS-CoV-2 variants with defined mutations that enhance pathogenicity or facilitate immune evasion has resulted in a continual decline in the protective efficacy of existing vaccines. Therefore, there is a pressing need for a vaccine capable of combating future variants. In this study, we designed new mRNA vaccines, BSCoV05 and BSCoV06, and generated point mutations in the receptor-binding domain (RBD) of the original Wuhan strain to increase their broad-spectrum antiviral activity. Additionally, we used the BA.1 RBD as a control. Both vaccines elicited a robust immune response in BALB/c and K18-hACE2 mice, generating high levels of specific binding antibodies against the BA.2 RBD. Moreover, all three vaccines induced neutralizing antibodies against the prototype viral strain and relevant variants, including the Alpha and Beta strains and the Omicron variants BA.1, BA.2, BA.5, XBB.1.5, XBB.1.16, EG.5.1, and EG.5.1.1, with BSCoV06 demonstrating broader neutralizing antibody activity. Both BSCoV05 and BSCoV06 also elicited a cellular immune response. After the challenge, both BSCoV05 and BSCOV06 provided protection against the EG.5.1 strain in both mouse strains. Therefore, these two vaccines merit further evaluation in nonhuman primates, and this vaccine design strategy should be explored for its potential application in combating future SARS-CoV-2 variants, offering valuable insights into broad-spectrum vaccine development.https://doi.org/10.1038/s41541-025-01066-4 |
| spellingShingle | Xiaoming Liang Yuxia Yuan Junbin Wang Cong Tang Yun Yang Yanan Zhou Hao Yang Qing Huang Wenhai Yu Haixuan Wang Yuhuan Yan Dongdong Lin Yanwen Li Xuena Du Longhai Yuan Wenqi Quan Daoju Wu Shuaiyao Lu mRNA vaccines with RBD mutations have broad-spectrum activity against SARS-CoV-2 variants in mice npj Vaccines |
| title | mRNA vaccines with RBD mutations have broad-spectrum activity against SARS-CoV-2 variants in mice |
| title_full | mRNA vaccines with RBD mutations have broad-spectrum activity against SARS-CoV-2 variants in mice |
| title_fullStr | mRNA vaccines with RBD mutations have broad-spectrum activity against SARS-CoV-2 variants in mice |
| title_full_unstemmed | mRNA vaccines with RBD mutations have broad-spectrum activity against SARS-CoV-2 variants in mice |
| title_short | mRNA vaccines with RBD mutations have broad-spectrum activity against SARS-CoV-2 variants in mice |
| title_sort | mrna vaccines with rbd mutations have broad spectrum activity against sars cov 2 variants in mice |
| url | https://doi.org/10.1038/s41541-025-01066-4 |
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