Human herpesvirus 6 (HHV-6) infects over 90% of people. The HHV-6 subtype, HHV-6B in particular, is often associated with exanthem subitum in early childhood. Exanthem subitum is usually self-limiting and good prognosis disease; however, some infants primarily infected with HHV-6B develop encephalitis/encephalopathy, and half of the patients developed encephalopathy reported to have neurological sequelae. Furthermore, after primary infection, HHV-6B remains in a latent state and sometimes reactivated in immunosuppressed patients, causing life-threatening severe encephalopathy. However, effective immunotherapies or vaccines for controlling HHV-6B infection and reactivation have not yet been established. Recently, we have found that the HHV-6B tetrameric glycoprotein (g) complex, gH/gL/gQ1/gQ2 is a promising vaccine candidate, and currently under preclinical development. To confirm our vaccine candidate protein complex induce detectable T-cell responses, in this study, we comprehensively screened CD4⁺ and CD8⁺ T-cell epitopes in the gH/gL/gQ1/gQ2 tetrameric complex protein in mice immunisation model. Both BALB/c and C57BL/6 mice were immunised with the tetrameric complex protein or plasmid DNA encoding gH, gL, gQ1, and gQ2, and then restimulated with 162 20-mer peptides covering the whole gH/gL/gQ1/gQ2 sequences; multiple CD4⁺ and CD8⁺ T-cell-stimulating peptides were identified in both BALB/c and C57BL/6 mice. Our study demonstrates that gH/gL/gQ1/gQ2 tetramer-targeted vaccination has potential to induce T-cell responses in two different strains of mice and supports the future development and application of T-cell-inducing vaccine and immunotherapies against HHV-6B.

中文翻译：

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人疱疹病毒6B糖蛋白H / L / Q1 / Q2四聚体复合物中的小鼠T细胞表位的全面筛选。

人类疱疹病毒6（HHV-6）感染超过90％的人。HHV-6亚型，特别是HHV-6B，在儿童早期经常与发散亚群有关。下肢发散通常是自限性的且预后良好的疾病；然而，一些主要感染HHV-6B的婴儿发展为脑炎/脑病，据报道，一半的发展为脑病的患者患有神经系统后遗症。此外，在初次感染后，HHV-6B保持潜伏状态，有时在免疫抑制的患者中重新激活，从而导致危及生命的严重脑病。但是，尚未建立用于控制HHV-6B感染和再激活的有效免疫疗法或疫苗。最近，我们发现HHV-6B四聚体糖蛋白（g）复合物gH / gL / gQ1 / gQ2是很有前途的疫苗候选者，并且目前处于临床前开发阶段。为了确认我们的候选疫苗蛋白复合物诱导可检测的T细胞反应，在本研究中，我们全面筛选了CD4小鼠免疫模型中gH / gL / gQ1 / gQ2四聚体复合蛋白中的⁺和CD8 ⁺ T细胞表位。用四聚体复合蛋白或编码gH，gL，gQ1和gQ2的质粒DNA免疫BALB / c和C57BL / 6小鼠，然后用162个覆盖整个gH / gL / gQ1 / gQ2序列的20-mer肽再刺激。在BALB / c和C57BL / 6小鼠中均鉴定出多种CD4 ⁺和CD8 ⁺ T细胞刺激肽。我们的研究表明，针对gH / gL / gQ1 / gQ2四聚体的疫苗接种有潜力在两种不同的小鼠品系中诱导T细胞反应，并支持T细胞诱导疫苗的未来开发和应用以及针对HHV-6B的免疫疗法。