Federal State Budgetary Institution "National Research Centre for Epidemiology and Microbiology named after the Honorary Academician N. F. Gamaleya" of the Ministry of Health of the Russian Federation, Moscow, Russia.
Department of Molecular Neuroimmune Signalling, Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, Moscow, Russia.
PLoS One. 2023 May 10;18(5):e0284823. doi: 10.1371/journal.pone.0284823. eCollection 2023.
Tick-borne encephalitis virus (TBEV) is one of the most threatening pathogens which affects the human central nervous system (CNS). TBEV circulates widely in Northern Eurasia. According to ECDC, the number of TBE cases increase annually. There is no specific treatment for the TBEV infection, thus vaccination is the main preventive measure. Despite the existence of several inactivated vaccines currently being licensed, the development of new TBEV vaccines remains a leading priority in countries endemic to this pathogen. Here we report new recombinant virus made by infectious subgenomic amplicon (ISA) approach using TBEV and yellow fever virus vaccine strain (YF17DD-UN) as a genetic backbone. The recombinant virus is capable of effective replication in mammalian cells and induce TBEV-neutralizing antibodies in mice. Unlike the original vector based on the yellow fever vaccine strain, chimeric virus became neuroinvasive in doses of 107-106 PFU and can be used as a model of flavivirus neuroinvasiveness, neurotropism and neurovirulence. These properties of hybrid structures are the main factors limiting their practical use as vaccines platforms.
蜱传脑炎病毒（TBEV）是一种严重威胁人类中枢神经系统（CNS）的病原体。TBEV 在北欧亚广泛传播。根据 ECDC 的数据，TBE 病例数量逐年增加。目前尚无针对 TBEV 感染的特定治疗方法，因此疫苗接种是主要的预防措施。尽管目前有几种灭活疫苗获得许可，但在该病原体流行的国家，开发新的 TBEV 疫苗仍然是首要任务。在这里，我们报告了一种使用 TBEV 和黄热病疫苗株（YF17DD-UN）作为遗传骨架的新型传染性亚基因组扩增子（ISA）方法制成的重组病毒。该重组病毒能够在哺乳动物细胞中有效复制，并在小鼠中诱导产生 TBEV 中和抗体。与基于黄热病疫苗株的原始载体不同，嵌合病毒在 107-106 PFU 的剂量下具有神经侵袭性，可作为黄病毒神经侵袭性、神经嗜性和神经毒力的模型。这些杂种结构的特性是限制其作为疫苗平台实际应用的主要因素。
