Institute of Chemical Biology and Fundamental Medicine, Siberian Branch of the Russian Academy of Sciences, Novosibirsk 630090, Russia.
Russian Federal State Unitary Company "Microgen Scientific Industrial Company for Immunobiological Medicines" of the Health Ministry of Russian Federation, Branch in Tomsk 634040, Russia.
Vaccine. 2020 Jun 2;38(27):4309-4315. doi: 10.1016/j.vaccine.2020.04.051. Epub 2020 May 12.
Tick-borne encephalitis virus (TBEV) is the most important tick-transmitted pathogen in the family Flaviviridae and causes one of the most severe human neuroinfections. In this study, a neutralizing mouse mAb 14D5, which was previously shown to have cross-reactive binding to several flaviviruses belonging to the TBEV group, was examined for its prophylactic and therapeutic effects in BALB/c mice infected with TBEV. Before and after infection, mice were administrated mAb 14D5 at doses 100 μg and 10 μg per mouse. mAb 14D5 showed clear protective efficacy when injected at the high dose one day after infection, with survival rates that were TBEV dose-dependent. Prophylactic administration of mAb 14D5 was more effective than post-exposure administration and complete protection was documented when the mAb was administered one day before infection. The protective efficacy of mAb 14D5 was significantly higher than that of the anti-TBE serum immunoglobulin. However, no protection was observed in mice received the low dose of mAb 14D5 independent of the timing of mAb injection and TBEV dose. The ability of species-matched mAb 14D5 to mediate TBEV infection in mice was also investigated, and the results indicated that mAb 14D5 did not augment TBEV infection independent of the time of mAb administration. The neutralizing epitope for mAb 14D5 was localized in domain III of glycoprotein E of TBEV in a region between residues 301-339, which is conserved among flaviviruses from the TBEV group.
蜱传脑炎病毒（TBEV）是黄病毒科中最重要的蜱传病原体，可引起最严重的人类神经感染之一。在本研究中，研究了先前显示对属于 TBEV 组的几种黄病毒具有交叉反应性结合的中和性小鼠 mAb 14D5，以评估其在 TBEV 感染 BALB/c 小鼠中的预防和治疗效果。在感染前后，以 100μg 和 10μg/只的剂量给小鼠施用 mAb 14D5。在感染后一天以高剂量注射 mAb 14D5 时，mAb 14D5 显示出明显的保护效果，其存活率与 TBEV 剂量有关。预防性给予 mAb 14D5 比暴露后给予更有效，当 mAb 在感染前一天给予时，可完全保护。mAb 14D5 的保护效果明显高于抗 TBE 血清免疫球蛋白。然而，无论 mAb 注射时间和 TBEV 剂量如何，接受低剂量 mAb 14D5 的小鼠均未观察到保护作用。还研究了种属匹配的 mAb 14D5 介导 TBEV 感染小鼠的能力，结果表明 mAb 14D5 不独立于 mAb 给药时间增强 TBEV 感染。mAb 14D5 的中和表位定位于 TBEV 糖蛋白 E 的 III 结构域中，位于残基 301-339 之间的区域，该区域在 TBEV 组的黄病毒中保守。
