Induction of neutralizing antibodies against hepatitis C virus by a subviral particle-based DNA vaccine
Induction of neutralizing antibodies against hepatitis C virus by a subviral particle-based DNA vaccine
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DOI：
10.1016/j.antiviral.2022.105266
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发表时间：
2022-02-28
影响因子：
7.6
通讯作者：
Suzuki, Ryosuke
中科院分区：
文献类型：
--
作者：
Yato, Keigo;Matsuda, Mami;Suzuki, Ryosuke
直接作用抗病毒药物(DAA)已被引入治疗丙型肝炎病毒(丙型肝炎病毒)；然而，仍然没有可用的疫苗来预防丙型肝炎病毒感染。我们之前报道了一种基于日本脑炎病毒(JEV)亚病毒颗粒(SVP)的疫苗，该疫苗在三个位置插入了丙型肝炎病毒E2中和表位(SVP-E2/Tri)。在本研究中，我们利用该SVP平台进行DNA免疫。此外，我们进一步探索了允许插入丙型肝炎病毒表位而不损害病毒组装和分泌的位置，以诱导更高滴度的中和抗体，并确定了三个新的外源表位插入位置。通过在5个位置插入丙型肝炎病毒表位(SVP-E_2/pENT)，成功地从转基因细胞中分泌出SVP。与SVP-E2/Tri相比，表达SVP-E2/pent的小鼠血清对丙型肝炎病毒具有更强的中和活性，而对乙脑病毒的中和活性较弱，这表明额外插入的丙型肝炎病毒表位有助于诱导针对插入多肽的抗体，而对乙脑病毒的中和表位被破坏。本研究提供了一种潜在有效的新型DNA疫苗平台。
Direct-acting antivirals (DAAs) have been introduced for the treatment of hepatitis C virus (HCV); however, there is still no available vaccine for preventing HCV infection. We previously reported on a Japanese encephalitis virus (JEV) subviral particle (SVP)-based vaccine with insertion of the HCV E2 neutralization epitope at three positions (SVP-E2/Tri). In this study, we utilized this SVP platform for DNA immunization. In addition, we explored further sites permitting the insertion of HCV epitopes without impairing viral assembly and secretion to elicit higher titers of neutralizing antibodies, and we identified three new positions for foreign epitope insertion. Successful secretion of SVPs with the insertion of HCV epitopes at five positions (SVP-E2/Pent) was seen from transfected cells. Compared to SVP-E2/Tri, sera from mice immunized with the plasmid expressing SVP-E2/Pent showed more neutralization activity against HCV, and less neutralization activity against JEV, suggesting that the additional insertion of HCV epitopes contributed to the induction of antibodies against the inserted peptide, whereas the neutralizing epitopes against JEV were disrupted. This study provides a potentially effective novel DNA vaccine platform.