State Key Laboratory of Biotherapy, Department of Anesthesiology and Translational Neuroscience Center, West China Hospital, Sichuan University and Collaborative Innovation Center for Biotherapy, Sichuan University, Chengdu, China.
School of Chemical and Pharmaceutical Engineering, Sichuan University of Science and Engineering, Zigong, China.
Front Immunol. 2019 Jan 10;9:3127. doi: 10.3389/fimmu.2018.03127. eCollection 2018.
Macrophage foam cells (FCs) play a crucial role in the initiation and progression of atherosclerosis. Reducing the formation or inducing the removal of FCs could ameliorate atherosclerosis. The present study examined whether the whole-cell vaccination using FCs could be used as novel prevention and treatment strategies to battle atherosclerosis. ApoE mice with initial or established atherosclerosis were subcutaneously immunized three times with FCs in Freund's adjuvant. Immunization with FCs resulted in an overt reduction of atherosclerotic lesion in the whole aorta and the aortic root with enhanced lesion stability. Subsequent study in mechanism showed that FCs vaccination dramatically increased CD4 T cell and CD8 T cell populations. Immunization with FCs significantly raised the plasma FCs-specific IgG antibodies. Of note, the FCs immune plasma could selectively recognize and bind to FC. FCs immune plasma significantly blocked the process of FCs formation, finally reduced the accumulation of FCs in plaque. Additionally, it was observed that FCs immunization down-regulated the expression level of atherosclerosis related pro-inflammatory cytokines, including IFN-γ, MCP-1, and IL-6 and enhanced the lesion stability with a significant increase in TGF-β1 level and collagen content. These findings demonstrate that the whole-cell vaccination using FCs significantly decreased lesion development and positively modulated lesion progression and stability by targeting FCs. The whole-cell FCs vaccine might represent a potential novel strategy for development of new antibodies and vaccines to the prevention or treatment of atherosclerosis.
泡沫细胞（FCs）在动脉粥样硬化的发生和发展中起着关键作用。减少 FCs 的形成或诱导其清除可以改善动脉粥样硬化。本研究探讨了使用 FCs 进行全细胞疫苗接种是否可以作为一种新的预防和治疗动脉粥样硬化的策略。
在初始或已建立动脉粥样硬化的载脂蛋白 E 小鼠中，用 FCs 在弗氏佐剂中进行三次皮下免疫接种。FCs 免疫接种导致整个主动脉和主动脉根部的动脉粥样硬化病变明显减少，并增强了病变的稳定性。随后的机制研究表明，FCs 疫苗接种显著增加了 CD4 T 细胞和 CD8 T 细胞群体。FCs 免疫接种显著提高了血浆 FCs 特异性 IgG 抗体水平。值得注意的是，FCs 免疫血浆可以选择性地识别和结合 FC。FCs 免疫血浆显著阻断了 FCs 形成的过程，最终减少了斑块中 FCs 的积累。此外，还观察到 FCs 免疫接种下调了与动脉粥样硬化相关的促炎细胞因子的表达水平，包括 IFN-γ、MCP-1 和 IL-6，并通过显著增加 TGF-β1 水平和胶原含量来增强病变的稳定性。
这些发现表明，使用 FCs 进行全细胞疫苗接种可显著减少病变发展，并通过靶向 FCs 积极调节病变进展和稳定性。全细胞 FCs 疫苗可能代表了开发用于预防或治疗动脉粥样硬化的新抗体和疫苗的一种潜在新策略。
