CHIKV mRNA vaccines encoding conserved structural/envelope proteins confer broad cross-lineage protection against infection
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.
Authors
- Hao Yang (ORCID: https://orcid.org/0000-0002-6580-534X)
- Bai Li (ORCID: https://orcid.org/0000-0002-5412-6106)
- Wenqi Quan
- Yuhuan Yan
- Youchun Wang (ORCID: https://orcid.org/0000-0001-9769-5141)
- Jian Zhou (ORCID: https://orcid.org/0000-0002-7061-5815)
- Xianhong Du (ORCID: https://orcid.org/0009-0009-6146-3993)
- Qiangming Sun (ORCID: https://orcid.org/0000-0003-1376-3827)
- Haixuan Wang
- Qing Huang (ORCID: https://orcid.org/0000-0002-8031-2578)
- Shuaiyao Lu (ORCID: https://orcid.org/0000-0003-1675-9735)
- Dongdong Lin (ORCID: https://orcid.org/0000-0002-7525-7973)
- Ran An (ORCID: https://orcid.org/0000-0003-2192-7553)
- Wenhai Yu (ORCID: https://orcid.org/0000-0002-3205-2062)
- Qianqian Li (ORCID: https://orcid.org/0000-0002-7508-2130)
- Yun Yang (ORCID: https://orcid.org/0000-0002-9986-5930)
- Yanan Zhou (ORCID: https://orcid.org/0000-0002-7724-9942)
- Yan-Wen Li (ORCID: https://orcid.org/0000-0002-4196-1751)
- Junbin Wang (ORCID: https://orcid.org/0000-0002-9668-0666)
- Cong Tang (ORCID: https://orcid.org/0000-0003-2718-2820)
- Lianxiong Yuan (ORCID: https://orcid.org/0000-0002-4622-1402)
- Xiaoming Liang (ORCID: https://orcid.org/0009-0001-3438-0027)
- Yuxia Yuan
- Hongyu Chen (ORCID: https://orcid.org/0000-0002-5325-9249)
- Yong Zhang (ORCID: https://orcid.org/0009-0009-7948-512X)
Institutions
- Oklahoma State Department of Health (US)
- Chinese Academy of Medical Sciences & Peking Union Medical College (CN)
- Vector & Vector-Borne Diseases Research Institute (TZ)
- Ministry of Education (RO)
- Ministry of Education (SA)
- Yunnan Center for Disease Control And Prevention (CN)
- China National Health Development Research Center (CN)
Publication Details
- Journal
- Signal Transduction and Targeted Therapy
- Published
- 2025-03-28
- DOI
- https://doi.org/10.1038/s41392-025-02182-2
- Citations
- 5
- Primary Topic
- Mosquito-borne diseases and control
- Type
- article
- Field-Weighted Citation Impact
- 9.39