CHIKV mRNA vaccines encoding conserved structural/envelope proteins confer broad cross-lineage protection against infection
Abstract With the broad spread of the chikungunya virus (CHIKV), there is an increasing demand for more effective and broadly protective vaccines. Here, we designed CHIKV mRNA vaccines containing full-length structural proteins or part of structural proteins (envelope proteins) based on conserved se...
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| Format: | Article |
| Language: | English |
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Nature Publishing Group
2025-03-01
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| Series: | Signal Transduction and Targeted Therapy |
| Online Access: | https://doi.org/10.1038/s41392-025-02182-2 |
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| author | Xiaoming Liang Yanan Zhou Yun Yang Qianqian Li Junbin Wang Bai Li Hao Yang Cong Tang Wenhai Yu Haixuan Wang Qing Huang Hongyu Chen Yuhuan Yan Ran An Dongdong Lin Wenqi Quan Yong Zhang Yanwen Li Xuena Du Yuxia Yuan Longhai Yuan Jian Zhou Qiangming Sun Youchun Wang Shuaiyao Lu |
| author_facet | Xiaoming Liang Yanan Zhou Yun Yang Qianqian Li Junbin Wang Bai Li Hao Yang Cong Tang Wenhai Yu Haixuan Wang Qing Huang Hongyu Chen Yuhuan Yan Ran An Dongdong Lin Wenqi Quan Yong Zhang Yanwen Li Xuena Du Yuxia Yuan Longhai Yuan Jian Zhou Qiangming Sun Youchun Wang Shuaiyao Lu |
| author_sort | Xiaoming Liang |
| collection | DOAJ |
| description | Abstract With the broad spread of the chikungunya virus (CHIKV), there is an increasing demand for more effective and broadly protective vaccines. Here, we designed CHIKV mRNA vaccines containing full-length structural proteins or part of structural proteins (envelope proteins) based on conserved sequences from 769 viral strains encompassing four lineages. The vaccine induced strong cellular and humoral immune responses in BALB/c mice and provided robust protection. Immunization of BALB/c mice with either of the two vaccines induced high levels of neutralizing antibodies against pseudoviruses from four distinct lineages, highlighting their potential for broad cross-lineage protective efficacy. Immunoglobulin repertoire analysis revealed two important BCR V-J gene combinations, IgHV1-4-IgHJ3 and IgHV1-4-IgHJ2, and lineage-specific immunity analysis revealed significant upregulation of TCRs containing V19 and V20. BCR and TCR immunodiversity may be a potential reason for the broad-spectrum protection against CHIKV afforded by the vaccine. In A129 mice, it elicited lower levels of neutralizing antibodies but prevented mouse mortality and cleared chronic infection. In the rhesus macaque model, both vaccines elicited a certain level of humoral and cellular immune responses and protected the rhesus macaques from the CHIKV challenge. In conclusion, the results from both mouse and rhesus macaque models indicate that the vaccine could be a candidate for clinical use against CHIKV. |
| format | Article |
| id | doaj-art-fccc056ee9be40c99681c28e94d4e8ca |
| institution | DOAJ |
| issn | 2059-3635 |
| language | English |
| publishDate | 2025-03-01 |
| publisher | Nature Publishing Group |
| record_format | Article |
| series | Signal Transduction and Targeted Therapy |
| spelling | doaj-art-fccc056ee9be40c99681c28e94d4e8ca2025-08-20T02:49:06ZengNature Publishing GroupSignal Transduction and Targeted Therapy2059-36352025-03-0110111510.1038/s41392-025-02182-2CHIKV mRNA vaccines encoding conserved structural/envelope proteins confer broad cross-lineage protection against infectionXiaoming Liang0Yanan Zhou1Yun Yang2Qianqian Li3Junbin Wang4Bai Li5Hao Yang6Cong Tang7Wenhai Yu8Haixuan Wang9Qing Huang10Hongyu Chen11Yuhuan Yan12Ran An13Dongdong Lin14Wenqi Quan15Yong Zhang16Yanwen Li17Xuena Du18Yuxia Yuan19Longhai Yuan20Jian Zhou21Qiangming Sun22Youchun Wang23Shuaiyao Lu24Yunnan Key Laboratory of Cross-Border Infectious Disease Control and Prevention and Novel Drug Development, Institute of Medical Biology, Chinese Academy of Medical Sciences and Peking Union Medical CollegeYunnan Key Laboratory of Cross-Border Infectious Disease Control and Prevention and Novel Drug Development, Institute of Medical Biology, Chinese Academy of Medical Sciences and Peking Union Medical CollegeYunnan Key Laboratory of Cross-Border Infectious Disease Control and Prevention and Novel Drug Development, Institute of Medical Biology, Chinese Academy of Medical Sciences and Peking Union Medical CollegeYunnan Key Laboratory of Cross-Border Infectious Disease Control and Prevention and Novel Drug Development, Institute of Medical Biology, Chinese Academy of Medical Sciences and Peking Union Medical CollegeYunnan Key Laboratory of Cross-Border Infectious Disease Control and Prevention and Novel Drug Development, Institute of Medical Biology, Chinese Academy of Medical Sciences and Peking Union Medical CollegeYunnan Key Laboratory of Cross-Border Infectious Disease Control and Prevention and Novel Drug Development, Institute of Medical Biology, Chinese Academy of Medical Sciences and Peking Union Medical CollegeYunnan Key Laboratory of Cross-Border Infectious Disease Control and Prevention and Novel Drug Development, Institute of Medical Biology, Chinese Academy of Medical Sciences and Peking Union Medical CollegeYunnan Key Laboratory of Cross-Border Infectious Disease Control and Prevention and Novel Drug Development, Institute of Medical Biology, Chinese Academy of Medical Sciences and Peking Union Medical CollegeYunnan Key Laboratory of Cross-Border Infectious Disease Control and Prevention and Novel Drug Development, Institute of Medical Biology, Chinese Academy of Medical Sciences and Peking Union Medical CollegeYunnan Key Laboratory of Cross-Border Infectious Disease Control and Prevention and Novel Drug Development, Institute of Medical Biology, Chinese Academy of Medical Sciences and Peking Union Medical CollegeYunnan Key Laboratory of Cross-Border Infectious Disease Control and Prevention and Novel Drug Development, Institute of Medical Biology, Chinese Academy of Medical Sciences and Peking Union Medical CollegeYunnan Key Laboratory of Cross-Border Infectious Disease Control and Prevention and Novel Drug Development, Institute of Medical Biology, Chinese Academy of Medical Sciences and Peking Union Medical CollegeYunnan Key Laboratory of Cross-Border Infectious Disease Control and Prevention and Novel Drug Development, Institute of Medical Biology, Chinese Academy of Medical Sciences and Peking Union Medical CollegeYunnan Key Laboratory of Cross-Border Infectious Disease Control and Prevention and Novel Drug Development, Institute of Medical Biology, Chinese Academy of Medical Sciences and Peking Union Medical CollegeYunnan Key Laboratory of Cross-Border Infectious Disease Control and Prevention and Novel Drug Development, Institute of Medical Biology, Chinese Academy of Medical Sciences and Peking Union Medical CollegeYunnan Key Laboratory of Cross-Border Infectious Disease Control and Prevention and Novel Drug Development, Institute of Medical Biology, Chinese Academy of Medical Sciences and Peking Union Medical CollegeYunnan Key Laboratory of Cross-Border Infectious Disease Control and Prevention and Novel Drug Development, Institute of Medical Biology, Chinese Academy of Medical Sciences and Peking Union Medical CollegeYunnan Key Laboratory of Cross-Border Infectious Disease Control and Prevention and Novel Drug Development, Institute of Medical Biology, Chinese Academy of Medical Sciences and Peking Union Medical CollegeYunnan Key Laboratory of Cross-Border Infectious Disease Control and Prevention and Novel Drug Development, Institute of Medical Biology, Chinese Academy of Medical Sciences and Peking Union Medical CollegeYunnan Key Laboratory of Cross-Border Infectious Disease Control and Prevention and Novel Drug Development, Institute of Medical Biology, Chinese Academy of Medical Sciences and Peking Union Medical CollegeYunnan Key Laboratory of Cross-Border Infectious Disease Control and Prevention and Novel Drug Development, Institute of Medical Biology, Chinese Academy of Medical Sciences and Peking Union Medical CollegeYunnan Key Laboratory of Cross-Border Infectious Disease Control and Prevention and Novel Drug Development, Institute of Medical Biology, Chinese Academy of Medical Sciences and Peking Union Medical CollegeYunnan Key Laboratory of Cross-Border Infectious Disease Control and Prevention and Novel Drug Development, Institute of Medical Biology, Chinese Academy of Medical Sciences and Peking Union Medical CollegeYunnan Key Laboratory of Cross-Border Infectious Disease Control and Prevention and Novel Drug Development, Institute of Medical Biology, Chinese Academy of Medical Sciences and Peking Union Medical CollegeYunnan Key Laboratory of Cross-Border Infectious Disease Control and Prevention and Novel Drug Development, Institute of Medical Biology, Chinese Academy of Medical Sciences and Peking Union Medical CollegeAbstract With the broad spread of the chikungunya virus (CHIKV), there is an increasing demand for more effective and broadly protective vaccines. Here, we designed CHIKV mRNA vaccines containing full-length structural proteins or part of structural proteins (envelope proteins) based on conserved sequences from 769 viral strains encompassing four lineages. The vaccine induced strong cellular and humoral immune responses in BALB/c mice and provided robust protection. Immunization of BALB/c mice with either of the two vaccines induced high levels of neutralizing antibodies against pseudoviruses from four distinct lineages, highlighting their potential for broad cross-lineage protective efficacy. Immunoglobulin repertoire analysis revealed two important BCR V-J gene combinations, IgHV1-4-IgHJ3 and IgHV1-4-IgHJ2, and lineage-specific immunity analysis revealed significant upregulation of TCRs containing V19 and V20. BCR and TCR immunodiversity may be a potential reason for the broad-spectrum protection against CHIKV afforded by the vaccine. In A129 mice, it elicited lower levels of neutralizing antibodies but prevented mouse mortality and cleared chronic infection. In the rhesus macaque model, both vaccines elicited a certain level of humoral and cellular immune responses and protected the rhesus macaques from the CHIKV challenge. In conclusion, the results from both mouse and rhesus macaque models indicate that the vaccine could be a candidate for clinical use against CHIKV.https://doi.org/10.1038/s41392-025-02182-2 |
| spellingShingle | Xiaoming Liang Yanan Zhou Yun Yang Qianqian Li Junbin Wang Bai Li Hao Yang Cong Tang Wenhai Yu Haixuan Wang Qing Huang Hongyu Chen Yuhuan Yan Ran An Dongdong Lin Wenqi Quan Yong Zhang Yanwen Li Xuena Du Yuxia Yuan Longhai Yuan Jian Zhou Qiangming Sun Youchun Wang Shuaiyao Lu CHIKV mRNA vaccines encoding conserved structural/envelope proteins confer broad cross-lineage protection against infection Signal Transduction and Targeted Therapy |
| title | CHIKV mRNA vaccines encoding conserved structural/envelope proteins confer broad cross-lineage protection against infection |
| title_full | CHIKV mRNA vaccines encoding conserved structural/envelope proteins confer broad cross-lineage protection against infection |
| title_fullStr | CHIKV mRNA vaccines encoding conserved structural/envelope proteins confer broad cross-lineage protection against infection |
| title_full_unstemmed | CHIKV mRNA vaccines encoding conserved structural/envelope proteins confer broad cross-lineage protection against infection |
| title_short | CHIKV mRNA vaccines encoding conserved structural/envelope proteins confer broad cross-lineage protection against infection |
| title_sort | chikv mrna vaccines encoding conserved structural envelope proteins confer broad cross lineage protection against infection |
| url | https://doi.org/10.1038/s41392-025-02182-2 |
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