Albert Einstein College of Medicine, 1300 Morris Park, Bronx, NY 10461, USA.
Vaccine. 2011 Apr 5;29(16):2910-7. doi: 10.1016/j.vaccine.2011.02.009. Epub 2011 Feb 21.
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.
几项研究强调了早期高度中和抗体反应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 分离株的天然可溶性 E2 (sE2) 与不同佐剂或佐剂组合免疫的小鼠中的抗体反应。用弗氏佐剂、单磷酰脂质 A (MPL)、胞嘧啶磷酸硫代鸟嘌呤寡脱氧核苷酸 (CpG ODN) 或 α-半乳糖神经酰胺 (αGalCer) 衍生物佐剂化 sE2 仅引起适度的抗体反应。相比之下，用 sE2 和 QuilA 免疫会引起异常高的抗 E2 抗体滴度。这些小鼠的血清可有效中和 HCV 假病毒 (HCVpp) 1a 进入。此外，QuilA 和 CpG ODN 的组合进一步增强了中和抗体滴度，观察到对 HCVpp 4 的交叉中和。我们得出结论，QuilA 和 CpG ODN 的组合是一种有前途的佐剂组合，应进一步探索用于开发 HCV 亚单位疫苗。我们的工作还强调，佐剂和免疫原的理想组合必须通过经验确定。
