Liang Xiaoming, Zhou Yanan, Yang Yun, Li Qianqian, Wang Junbin, Li Bai, Yang Hao, Tang Cong, Yu Wenhai, Wang Haixuan, Huang Qing, Chen Hongyu, Yan Yuhuan, An Ran, Lin Dongdong, Quan Wenqi, Zhang Yong, Li Yanwen, Du Xuena, Yuan Yuxia, Yuan Longhai, Zhou Jian, Sun Qiangming, Wang Youchun, Lu Shuaiyao
Yunnan 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 College, Kunming, China.
State Key Laboratory of Respiratory Health and Multimorbidity, Beijing, China.
Signal Transduct Target Ther. 2025 Mar 28;10(1):98. doi: 10.1038/s41392-025-02182-2.
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.
随着基孔肯雅病毒（CHIKV）的广泛传播，对更有效且具有广泛保护作用的疫苗的需求日益增加。在此，我们基于来自涵盖四个谱系的769个病毒株的保守序列，设计了包含全长结构蛋白或部分结构蛋白（包膜蛋白）的CHIKV mRNA疫苗。该疫苗在BALB/c小鼠中诱导了强烈的细胞免疫和体液免疫反应，并提供了强大的保护作用。用这两种疫苗中的任何一种对BALB/c小鼠进行免疫接种，均可诱导产生针对来自四个不同谱系的假病毒的高水平中和抗体，突出了它们具有广泛的跨谱系保护效力的潜力。免疫球蛋白库分析揭示了两种重要的BCR V-J基因组合，即IgHV1-4-IgHJ3和IgHV1-4-IgHJ2，谱系特异性免疫分析显示含有V19和V20的TCR有显著上调。BCR和TCR免疫多样性可能是该疫苗对CHIKV提供广谱保护的一个潜在原因。在A129小鼠中，它诱导产生的中和抗体水平较低，但可预防小鼠死亡并清除慢性感染。在恒河猴模型中，两种疫苗均引发了一定水平的体液免疫和细胞免疫反应，并保护恒河猴免受CHIKV攻击。总之，小鼠和恒河猴模型的结果均表明，该疫苗可能是一种用于临床对抗CHIKV的候选疫苗。
