State Key Laboratory of Virology, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan, China.
University of the Chinese Academy of Sciences, Beijing, China.
J Virol. 2024 Jul 23;98(7):e0076924. doi: 10.1128/jvi.00769-24. Epub 2024 Jun 3.
Highly pathogenic viruses from family , which are mainly transmitted by arthropods, have intermittently sparked epidemics worldwide. In particular, tick-borne bandaviruses, such as severe fever with thrombocytopenia syndrome virus (SFTSV), continue to spread in mountainous areas, resulting in an average mortality rate as high as 10.5%, highlighting the urgency and importance of vaccine development. Here, an mRNA vaccine developed based on the full-length SFTSV glycoprotein, containing both the receptor-binding domain and the fusion domain, was shown to confer complete protection against SFTSV at a very low dose by triggering a type 1 helper T cell-biased cellular immune response in rodents. Moreover, the vaccine candidate elicited long-term immunity and protection against SFTSV for at least 5 months. Notably, it provided complete cross-protection against other bandaviruses, such as the Heartland virus and Guertu virus, in lethal challenge models. Further research revealed that the conserved epitopes among bandaviruses within the full-length SFTSV glycoprotein may facilitate broad-spectrum protection mediated by the cellular immune response. Collectively, these findings demonstrate that the full-length SFTSV glycoprotein mRNA vaccine is a promising vaccine candidate for SFTSV and other bandaviruses, and provide guidance for the development of broad-spectrum vaccines from conserved antigens and epitopes.
Tick-borne bandaviruses, such as SFTSV and Heartland virus, sporadically trigger outbreaks in addition to influenza viruses and coronaviruses, yet there are no specific vaccines or therapeutics against them. mRNA vaccine technology has advantages in terms of enabling expression and triggering cellular immunity, thus offering new solutions for vaccine development against intractable viruses, such as bandaviruses. In this study, we developed a novel vaccine candidate for SFTSV by employing mRNA vaccination technology and using a full-length glycoprotein as an antigen target. This candidate vaccine confers complete and durable protection against SFTSV at a notably low dose while also providing cross-protection against Heartland virus and Guertu virus. This study highlights the prospective value of full-length SFTSV-glycoprotein-based mRNA vaccines and suggests a potential strategy for broad-spectrum bandavirus vaccines.
家族中的高致病性病毒主要通过节肢动物传播，间歇性地在全球引发疫情。特别是蜱传班达病毒，如严重发热伴血小板减少综合征病毒（SFTSV），继续在山区传播，死亡率高达 10.5%，凸显了疫苗开发的紧迫性和重要性。在这里，一种基于 SFTSV 全长糖蛋白的 mRNA 疫苗被开发出来，该糖蛋白包含受体结合域和融合域，通过在啮齿动物中引发 1 型辅助 T 细胞偏向的细胞免疫反应，以非常低的剂量对 SFTSV 提供完全保护。此外，该疫苗候选物在至少 5 个月内引发了针对 SFTSV 的长期免疫和保护。值得注意的是，它在致死性挑战模型中对其他班达病毒，如 Heartland 病毒和 Guertu 病毒，提供了完全的交叉保护。进一步的研究表明，SFTSV 全长糖蛋白中的班达病毒之间的保守表位可能有助于细胞免疫反应介导的广谱保护。总的来说，这些发现表明，全长 SFTSV 糖蛋白 mRNA 疫苗是 SFTSV 和其他班达病毒的一种有前途的疫苗候选物，并为基于保守抗原和表位的广谱疫苗的开发提供了指导。
除了流感病毒和冠状病毒外，蜱传班达病毒，如 SFTSV 和 Heartland 病毒，也会偶尔引发爆发，但目前尚无针对它们的特定疫苗或疗法。mRNA 疫苗技术在表达和触发细胞免疫方面具有优势，因此为开发针对顽固病毒（如班达病毒）的疫苗提供了新的解决方案。在这项研究中，我们使用 mRNA 疫苗技术和全长糖蛋白作为抗原靶标，开发了一种针对 SFTSV 的新型疫苗候选物。该候选疫苗以明显低的剂量对 SFTSV 提供完全和持久的保护，同时对 Heartland 病毒和 Guertu 病毒提供交叉保护。这项研究突出了基于全长 SFTSV-糖蛋白的 mRNA 疫苗的潜在价值，并为广谱班达病毒疫苗提供了一种潜在策略。
