Hepatitis C virus soluble E2 in combination with QuilA and CpG ODN induces neutralizing antibodies in mice.
Hepatitis C virus soluble E2 in combination with QuilA and CpG ODN induces neutralizing antibodies in mice.
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DOI：
10.1016/j.vaccine.2011.02.009
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发表时间：
2011-04
期刊：
影响因子：
5.5
通讯作者：
M. Naarding;E. Falkowska;Hui Xiao;T. Dragic
中科院分区：
文献类型：
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作者：
M. Naarding;E. Falkowska;Hui Xiao;T. Dragic
几项研究强调了早期高度中和抗体应答在清除丙型肝炎病毒（HCV）感染中的重要性。包膜糖蛋白E2是HCV中和抗体的主要靶标。在这里，我们比较了用来自H77 1a分离物的天然可溶性E2（sE 2）与不同佐剂或佐剂组合偶联免疫的小鼠中的抗体应答。用弗氏、单磷酰脂质A（MPL）、胞嘧啶硫代磷酸鸟嘌呤寡脱氧核苷酸（CpG ODN）或α-半乳糖神经酰胺（αGalCer）衍生物佐剂sE 2仅引起中度抗体应答。相比之下，用sE 2和基拉免疫引起异常高的抗E2抗体滴度。来自这些小鼠的血清有效地中和HCV假颗粒（HCVpp）1a进入。此外，基拉和CpG ODN的组合进一步增强中和抗体滴度，其中观察到HCVpp 4的交叉中和。我们的结论是，基拉和CpG ODN的组合是一个很有前途的佐剂组合，应进一步探讨HCV亚单位疫苗的发展。我们的工作还强调，佐剂和免疫原的理想组合必须根据经验确定。
Several studies have emphasized the importance of an early, highly neutralizing antibody response in the clearance of Hepatitis C virus (HCV) infection. The envelope glycoprotein E2 is a major target for HCV neutralizing antibodies. Here, we compared antibody responses in mice immunized with native soluble E2 (sE2) from the H77 1a isolate coupled with different adjuvants or combinations of adjuvants. Adjuvanting sE2 with Freund's, monophosphoryl lipid A (MPL), cytosine phosphorothioate guanine oligodeoxynucleotide (CpG ODN), or alpha-galactosylceramide (αGalCer) derivatives elicited only moderate antibody responses. In contrast, immunizations with sE2 and QuilA elicited exceptionally high anti-E2 antibody titers. Sera from these mice effectively neutralized HCV pseudoparticles (HCVpp) 1a entry. Moreover, the combination of QuilA and CpG ODN further enhanced neutralizing antibody titers wherein cross-neutralization of HCVpp 4 was observed. We conclude that the combination of QuilA and CpG ODN is a promising adjuvant combination that should be further explored for the development of an HCV subunit vaccine. Our work also emphasizes that the ideal combination of adjuvant and immunogen has to be determined empirically.