Zhang Jiaxing, Zhang Junqi, Wang Yanbo, Sun Yubo, Wang Yongkai, Wang Yueyue, Yang Duan, Qiao Xupeng, Liu Xiaoqian, Ding Jiaqi, Zhang Xiyang, Zhang Wenbiao, Wang Zhenjie, Hu Chenchen, Han Chenying, Liu Tianyue, Yang Shuya, Sun Yuanjie, Cheng Linfeng, Jiang Dongbo, Yang Kun
Department of Immunology, Basic Medicine School, Air-Force Medical University (The Fourth Military Medical University), Xi'an, China.
College of Life Sciences, Northwest University, Xi'an, China.
NPJ Vaccines. 2024 Oct 23;9(1):196. doi: 10.1038/s41541-024-00991-0.
Hemorrhagic fever with renal syndrome (HFRS) occurs throughout Eurasia with considerable morbidity and mortality. Currently, the absence of specific treatments or effective antiviral drugs for hantavirus infection makes developing safe and effective vaccines a high priority. Here, we report the development of three novel nucleic acid vaccine candidates, mRNA, naked DNA, and DNA encapsulated in lipid nanoparticles, encoding the glycoproteins of the Hantaan virus (HTNV). To comprehensively evaluate the potential of candidate HTNV nucleic acid vaccines in preventing HFRS, we focus on evaluating their immunogenicity and efficacy in mice and comparing them with an inactivated vaccine as the benchmark. Our findings reveal that all candidate vaccines activated instant and sustained immune responses, offering comparable in vivo protective efficacy to the inactivated vaccines. Notably, compared to the inactivated vaccine, mRNA vaccine induced stronger virus-specific T-helper 1 cell immune response, while DNA-LNP elicited higher levels of neutralizing antibodies in mice. These results mark a significant step in developing nucleic acid vaccines for HTNV, suggesting that sequential immunization with DNA and mRNA vaccines could further amplify the advantages of nucleic acid vaccines.
肾综合征出血热（HFRS）在欧亚大陆广泛流行，具有较高的发病率和死亡率。目前，由于缺乏针对汉坦病毒感染的特效治疗方法或有效抗病毒药物，开发安全有效的疫苗成为当务之急。在此，我们报告了三种新型核酸疫苗候选物的研发情况，即编码汉滩病毒（HTNV）糖蛋白的信使核糖核酸（mRNA）疫苗、裸DNA疫苗以及脂质纳米颗粒包裹的DNA疫苗。为全面评估候选HTNV核酸疫苗预防HFRS的潜力，我们着重评估了它们在小鼠体内的免疫原性和效力，并与作为基准的灭活疫苗进行比较。我们的研究结果表明，所有候选疫苗均能激活即时且持续的免疫反应，在体内提供与灭活疫苗相当的保护效力。值得注意的是，与灭活疫苗相比，mRNA疫苗诱导产生更强的病毒特异性辅助性T细胞1型免疫反应，而脂质纳米颗粒包裹的DNA疫苗在小鼠体内引发更高水平的中和抗体。这些结果标志着HTNV核酸疫苗研发取得了重要进展，表明DNA疫苗和mRNA疫苗序贯免疫可进一步放大核酸疫苗的优势。
