Division of Inflammation Biology, La Jolla Institute for Allergy and Immunology, La Jolla, CA, USA.
Department of Bioengineering, University of California San Diego, La Jolla, CA, USA.
Eur J Immunol. 2018 Sep;48(9):1580-1587. doi: 10.1002/eji.201847584. Epub 2018 Aug 12.
Vaccination with MHC-II-restricted peptides from Apolipoprotein B (ApoB) with complete and incomplete Freund's adjuvant (CFA/IFA) is known to protect mice from atherosclerosis. This vaccination induces antigen-specific IgG1 and IgG2c antibody responses and a robust CD4 T cell response in lymph nodes. However, CFA/IFA cannot be used in humans. To find a clinically applicable adjuvant, we tested the effect of vaccinating Apoe-deficient mice with ApoB peptide P6 (TGAYSNASSTESASY). In a broad screening experiment, Addavax, a squalene-based oil-in-water adjuvant similar to MF59, was the only adjuvant that showed similar efficacy as CFA/IFA. This was confirmed in a confirmation experiment for both the aortic arch and whole aorta analyzed by en face analysis after atherosclerotic lesion staining. Mechanistically, restimulated peritoneal cells from mice immunized with P6 in Addavax released significant amounts of IL-10. Unlike P6 in CFA/IFA, vaccination with P6 in Addavax did not induce any detectable IgG1 or IgG2c antibodies to P6. These data suggest that squalene-based adjuvants such as MF59 are good candidate adjuvants for developing a clinically effective atherosclerosis vaccine.
用载脂蛋白 B（ApoB）的 MHC-II 限制性肽与完全弗氏佐剂（CFA）和不完全弗氏佐剂（IFA）免疫接种已知可以保护小鼠免受动脉粥样硬化的侵害。这种疫苗接种会诱导淋巴结中抗原特异性 IgG1 和 IgG2c 抗体反应和强烈的 CD4 T 细胞反应。然而，CFA/IFA 不能用于人类。为了寻找一种临床适用的佐剂，我们测试了用 ApoB 肽 P6（TGAYSNASSTESASY）对 Apoe 缺陷小鼠进行疫苗接种的效果。在广泛的筛选实验中，Addavax，一种与 MF59 类似的角鲨烯基油包水佐剂，是唯一显示出与 CFA/IFA 相似功效的佐剂。在用 Addavax 免疫接种的 P6 进行的确认实验中，通过动脉粥样硬化病变染色后的全面分析，对主动脉弓和整个主动脉进行了分析，证实了这一点。从用 Addavax 中的 P6 免疫接种的小鼠的再刺激腹膜细胞中释放出大量的 IL-10。与 CFA/IFA 中的 P6 不同，用 Addavax 中的 P6 进行疫苗接种不会诱导任何可检测到的针对 P6 的 IgG1 或 IgG2c 抗体。这些数据表明，角鲨烯基佐剂如 MF59 是开发临床有效动脉粥样硬化疫苗的良好候选佐剂。
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