Department of Laboratory Medicine, First Affiliated Hospital, School of Medicine, Xi'an Jiaotong University, Xi'an 710061, Shaanxi, China.
Department of Pathology, School of Basic Medical Sciences, Health Science Center, Xi'an Jiaotong University, Xi'an 710061, Shaanxi, China; Therapeutic Vaccines Engineering Center of Shaanxi Province, Health Science Center, Xi'an Jiaotong University, Xi'an 710061, Shaanxi, China.
Int Immunopharmacol. 2018 Jan;54:95-102. doi: 10.1016/j.intimp.2017.10.020. Epub 2017 Nov 4.
Synthetic peptide cancer vaccines are poorly immunogenic sub-unit vaccines and thus essentially need adjuvants in their formulations to increase the efficacy by enhancing the peptide-specific immune response. However, aluminum-based compounds are almost dependent for clinical use at present. Therefore, the increasing use of peptide-based vaccines makes the need for novel and potent adjuvants. Polyactin A (PAA) has been used for the clinical treatment of impaired immunity in China for over 30years. To figure out the adjuvant effects of PAA for E75 peptide breast cancer vaccine (Her2 p369-p377), the generation of mature dendritic cells (DCs) from peripheral blood monocytes (PBMCs) cultured with PAA, IL-4 and TNF-α was assessed by morphologic features and the expressions of special surface markers using flow cytometry. Then the functional features of PBMCs-derived DCs cultured with PAA, IL-4 and TNF-α were investigated by inducing E75-specific cytotoxicity. Finally, C57BL/6-Tg(HLA-A2.1)1Enge/J transgenic mice were immunized with E75 and various amounts of PAA, and splenic lymphocyte proliferation and the IFN-γ level were determined. The results showed that PAA, just like granulocyte-macrophage colony stimulating factor, with IL-4 and TNF-α efficiently induced mature DCs from PBMCs, and these DCs could trigger a potent E75 peptide-specific CD8 T-cell response in vitro. Immunization with E75 and PAA significantly increased positive rates of CD4 and CD8 T lymphocytes, and enhanced splenocytes proliferation and levels of IFN-γ in splenocytes when induced by E75. Our results indicated that PAA could efficiently induce E75-specific immunologic responses in vitro and in vivo. Therefore, PAA possesses potent adjuvant effect on peptide-based cancer vaccine. Our study provides a safe, effective and novel adjuvant for clinical use.
合成肽癌症疫苗是免疫原性较差的亚单位疫苗，因此在其配方中基本上需要佐剂来增强肽特异性免疫应答，从而提高疗效。然而，目前基于铝的化合物几乎是临床应用所必需的。因此，肽基疫苗的使用越来越多，这就需要新型有效的佐剂。聚丙交酯 A (PAA) 在中国已用于临床治疗免疫受损超过 30 年。为了研究 PAA 对 E75 肽乳腺癌疫苗（Her2 p369-p377）的佐剂作用，我们通过形态学特征和流式细胞术检测特殊表面标志物的表达，评估了 PAA、IL-4 和 TNF-α 培养外周血单核细胞（PBMC）生成成熟树突状细胞（DC）的情况。然后，通过诱导 E75 特异性细胞毒性来研究 PAA、IL-4 和 TNF-α 培养的 PBMC 来源的 DC 的功能特征。最后，用 E75 和不同剂量的 PAA 免疫 C57BL/6-Tg(HLA-A2.1)1Enge/J 转基因小鼠，测定脾淋巴细胞增殖和 IFN-γ 水平。结果表明，PAA 与粒细胞-巨噬细胞集落刺激因子一样，与 IL-4 和 TNF-α 一起有效地从 PBMC 中诱导成熟的 DC，这些 DC 可以在体外引发强烈的 E75 肽特异性 CD8 T 细胞反应。用 E75 和 PAA 免疫可显著提高 CD4 和 CD8 T 淋巴细胞的阳性率，并增强 E75 诱导的脾细胞增殖和脾细胞 IFN-γ 水平。我们的研究结果表明，PAA 可以在体外和体内有效地诱导 E75 特异性免疫反应。因此，PAA 对基于肽的癌症疫苗具有强大的佐剂作用。本研究为临床应用提供了一种安全、有效、新颖的佐剂。
