Chernokhaeva L L, Rogova Yu V, Vorovitch M F, Romanova L Iu, Kozlovskaya L I, Maikova G B, Kholodilov I S, Karganova G G
Chumakov Institute of Poliomyelitis and Viral Encephalitides, Moscow 142782 Russia.
Chumakov Institute of Poliomyelitis and Viral Encephalitides, Moscow 142782 Russia.
Vaccine. 2016 Apr 29;34(20):2354-61. doi: 10.1016/j.vaccine.2016.03.041. Epub 2016 Mar 21.
Tick-borne encephalitis (TBE) circulates widely in the territory of Eurasia with up to 10,000 cases registered annually. The TBE virus (TBEV) includes three main subtypes: European, Siberian and Far-Eastern, and two new Asiatic variants, phylogenetically distant from the others. The inactivated antigen of European or Far-Eastern strains is used in commercial TBE vaccines. A set of 14 TBEV strains, isolated in 1937-2008, with different passage histories, representing all subtypes and variants, was used in this work. The chosen set covers almost all the TBE area. Sera of mice, immunized with the TBE vaccine Moscow, prepared from the TBEV strain Sofjin, were studied in a plaque neutralization test against the set of TBEV strains. The vaccine induced antibodies at a protective titer against all TBEV strains and Omsk hemorrhagic fever virus (OHFV) with Е protein amino acid distances of 0.008-0.069, but not against Powassan virus. We showed that after a course of two immunizations, factors such as the period between vaccinations (1-4 weeks), the challenging virus dose (30-1000 LD50) and terms of challenge (1-4 weeks after the last immunization) did not significantly affect the assessment of protective efficacy of the vaccine in vivo. The protective effect of the TBE vaccine Moscow against the set of TBEV strains and the OHFV was demonstrated in in vivo experiments. TBE vaccine Moscow did not protect mice against 10 LD50 of the Powassan virus. We showed that this range of Е protein amino acid distances between the vaccine strain and challenging virus do not have a decisive impact on the TBE vaccine protective effect in vitro and in vivo. Moreover, the TBE vaccine Moscow induces an immune response protective against a wide range of TBEV variants.
蜱传脑炎(TBE)在欧亚大陆广泛传播,每年报告的病例多达10000例。TBE病毒(TBEV)包括三个主要亚型:欧洲型、西伯利亚型和远东型,以及两个新的亚洲变种,它们在系统发育上与其他亚型相距较远。欧洲或远东毒株的灭活抗原用于商业化的TBE疫苗。本研究使用了一组14株TBEV毒株,这些毒株于1937年至2008年分离,具有不同的传代历史,代表了所有亚型和变种。所选毒株几乎覆盖了整个TBE流行区域。用从TBEV索夫金毒株制备的莫斯科TBE疫苗免疫的小鼠血清,在针对该组TBEV毒株的空斑中和试验中进行了研究。该疫苗诱导产生的抗体对所有TBEV毒株和鄂木斯克出血热病毒(OHFV)具有保护性滴度,E蛋白氨基酸距离为0.008 - 0.069,但对波瓦桑病毒无保护作用。我们发现,在进行两次免疫接种后,诸如两次接种之间的间隔时间(1 - 4周)、攻击病毒剂量(30 - 1000 LD50)以及攻击时间(最后一次免疫接种后1 - 4周)等因素,对疫苗在体内保护效果的评估没有显著影响。莫斯科TBE疫苗对该组TBEV毒株和OHFV的保护作用在体内实验中得到了证实。莫斯科TBE疫苗不能保护小鼠抵抗10 LD50的波瓦桑病毒。我们表明,疫苗毒株与攻击病毒之间的这种E蛋白氨基酸距离范围,对TBE疫苗在体外和体内的保护效果没有决定性影响。此外,莫斯科TBE疫苗能诱导针对多种TBEV变种的保护性免疫反应。