Immunological responses following administration of a genotype 1a/1b/2/3a quadrivalent HCV VLP vaccine.
Immunological responses following administration of a genotype 1a/1b/2/3a quadrivalent HCV VLP vaccine.
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DOI：
10.1038/s41598-018-24762-9
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发表时间：
2018-04-24
影响因子：
4.6
通讯作者：
Torresi J
中科院分区：
文献类型：
--
作者：
Christiansen D;Earnest-Silveira L;Chua B;Meuleman P;Boo I;Grubor-Bauk B;Jackson DC;Keck ZY;Foung SKH;Drummer HE;Gowans EJ;Torresi J
丙型肝炎病毒（HCV）的重大公共卫生问题已经部分解决了直接作用的抗病毒药物（DAA）的出现。然而，开发有效的预防性疫苗将对HCV发病率产生重大影响，并将代表全球控制和可能根除HCV的重大进展。我们以前报道了基因型1a HCV病毒样颗粒（VLP）疫苗，产生中和抗体（NAb）和T细胞对HCV的反应。为了推进这种方法，我们生产了四价基因型1a/1b/2a/3a HCV VLP疫苗，以产生更广泛的免疫应答。我们表明，这种四价疫苗产生抗体和NA B反应连同强烈的T和B细胞反应接种小鼠。此外，靶向E2蛋白的保守抗原结构域B和D表位的选择性中和人单克隆抗体（HuMAb）与HCV VLP强烈结合，表明这些关键表位在颗粒表面上表达。我们的研究结果表明，四价HCV VLP疫苗诱导广泛的体液和细胞免疫反应，这将是必要的保护对HCV。这种疫苗可以提供一个实质性的除了高活性的抗病毒药物在消除丙型肝炎病毒。
The significant public health problem of Hepatitis C virus (HCV) has been partially addressed with the advent of directly acting antiviral agents (DAAs). However, the development of an effective preventative vaccine would have a significant impact on HCV incidence and would represent a major advance towards controlling and possibly eradicating HCV globally. We previously reported a genotype 1a HCV viral-like particle (VLP) vaccine that produced neutralizing antibodies (NAb) and T cell responses to HCV. To advance this approach, we produced a quadrivalent genotype 1a/1b/2a/3a HCV VLP vaccine to produce broader immune responses. We show that this quadrivalent vaccine produces antibody and NAb responses together with strong T and B cell responses in vaccinated mice. Moreover, selective neutralizing human monoclonal antibodies (HuMAbs) targeting conserved antigenic domain B and D epitopes of the E2 protein bound strongly to the HCV VLPs, suggesting that these critical epitopes are expressed on the surface of the particles. Our findings demonstrate that a quadrivalent HCV VLP based vaccine induces broad humoral and cellular immune responses that will be necessary for protection against HCV. Such a vaccine could provide a substantial addition to highly active antiviral drugs in eliminating HCV.
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