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Evaluation of immune response and protective effect of four vaccines against the tick-borne encephalitis virus

机译:四种疫苗对the传脑炎病毒的免疫应答和保护作用的评估

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Among three main subtypes of the tick-borne encephalitis virus (TBEV), the Siberian subtype is currently dominant in a majority of the endemic regions of Russia. However, inactivated vaccines are based on TBEV strains of the heterologous Far Eastern or the European subtypes isolated 40-77 years ago. To analyze the efficacy of the available vaccines against currently prevailing TBEV isolates of the Siberian subtype, mice were immunized subcutaneously three times (one group per each vaccine). The expression of seven cytokine genes was determined using RT-PCR. Sera were studied using homologous and heterologous ELISA, hemagglutination inhibition (HI) and neutralization tests with TBEV strains of the Far Eastern, Siberian and European subtypes. Cross-protective efficacy of the vaccines was evaluated with the TBEV strain 2689 of Siberian subtype isolated from an ixodid tick from the Novosibirsk, South-Western Siberia, Russia in 2010. The cytokine gene expression profile indicates a predominantly Th2 response due to exogenous antigen presentation. Titers for homologous combinations of vaccine strain and strain in ELISA, HI and neutralization tests exceeded those for heterologous antigen-antibody pairs. Despite antibody detection by means of ELISA, HI and neutralization tests, the mouse protection afforded by the vaccines differed significantly. Complete protection of mice challenged with 100 LD50 virus of the Siberian subtype was induced by the vaccine "Encevir" ("Microgen", Tomsk, Russia). The minimal immunization doze (MID50) of "Encevir" protecting 50% of the mice was less than 0.0016 ml. Partial protective effect of vaccines produced in Moscow, Russia and Austria revealed MID50 within recommended intervals (0.001-0.017 ml). However, the MID50 for the vaccine "Encepur" (Novartis, Germany) 0.04 ml exceeded acceptable limits with total loss of mice immunized with vaccine diluted 32,100 and 320 fold. These results suggest regular evaluation of TBEV vaccines in regions where heterologous virus subtypes prevail
机译:在the传播性脑炎病毒(TBEV)的三种主要亚型中,西伯利亚亚型目前在俄罗斯大多数流行地区中占主导地位。但是,灭活疫苗是基于40-77年前分离的异源远东或欧洲亚型的TBEV株。为了分析可用疫苗针对目前流行的西伯利亚亚型TBEV分离株的功效,将小鼠皮下免疫3次(每种疫苗一组)。使用RT-PCR确定七个细胞因子基因的表达。使用远东,西伯利亚和欧洲亚型的TBEV菌株,通过同源和异源ELISA,血凝抑制(HI)和中和测试研究了血清。用2010年从俄罗斯西伯利亚西南部新西伯利亚的ixodd壁虱分离的西伯利亚亚型TBEV菌株2689评估了疫苗的交叉保护功效。细胞因子基因表达谱表明,由于外源抗原呈递,主要是Th2反应。 ELISA,HI和中和测试中疫苗株和菌株的同源组合滴度超过了异源抗原-抗体对的滴度。尽管通过ELISA,HI和中和测试检测到抗体,但疫苗提供的小鼠保护作用却存在显着差异。疫苗“ Encevir”(“ Microgen”,俄罗斯托木斯克)诱导了对西伯利亚亚型100 LD50病毒攻击的小鼠的完全保护。保护50%小鼠的“ Encevir”的最小免疫休眠(MID50)小于0.0016ml。在莫斯科,俄罗斯和奥地利生产的疫苗的部分保护作用表明MID50在建议的间隔内(0.001-0.017 ml)。但是,疫苗“ Encepur”(德国诺瓦蒂斯)的MID50超过了可接受的极限,用32,100和320倍稀释的疫苗免疫的小鼠全部丧失。这些结果表明在异源病毒亚型盛行的地区定期评估TBEV疫苗

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