Vaccination provides a promising approach for treatment of hypercholesterolemia and improvement in compliance. In this study, the appropriate virus-like particle (VLP)-peptide vaccines targeting proprotein convertase subtilisin/kexin type 9 (PCSK9) were screened. The screening criteria of target peptides were as follows: (1) located in catalytic domain of PCSK9, or regulating the binding of PCSK9 and LDL receptors (LDLR); (2) having low/no-similarity when matched with the host proteome; (3) possessing ideal antigenicity and hydrophilicity; (4) including the functional mutation site of PCSK9. It was found that mice vaccinated with VLP -PCSK9 peptide vaccines, especially PCSK9Qβ-003 vaccine, developed high titer IgG antibodies against PCSK9. PCSK9Qβ-003 vaccine obviously decreased plasma total cholesterol in both Balb/c mice and LDLR^+/- mice. Also, PCSK9Qβ-003 vaccine decreased plasma PCSK9 level and up-regulated LDLR expression in liver. Additionally, PCSK9Qβ-003 vaccine injection was associated with significant up-regulation of sterol-regulatory element-binding protein-2 (SREBP-2), hepatocyte nuclear factor 1α (HNF-1α), and 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase in LDLR^+/- mice. No obvious immune injury was detected in vaccinated animals. The PCSK9Qβ-003 vaccine, therefore, may be an attractive treatment approach for hypercholesterolemia through decreasing cholesterol and regulating lipid homeostasis.

中文翻译：

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针对PCSK9的治疗性肽疫苗。

疫苗接种为治疗高胆固醇血症和改善依从性提供了一种有前途的方法。在这项研究中，筛选了针对原蛋白转化酶枯草杆菌蛋白酶/ kexin 9型（PCSK9）的合适的病毒样颗粒（VLP）-肽疫苗。靶肽的筛选标准如下：（1）位于PCSK9的催化域，或调节PCSK9与LDL受体（LDLR）的结合；（2）与宿主蛋白质组匹配时具有低/无相似性；（3）具有理想的抗原性和亲水性；（4）包括PCSK9的功能突变位点。发现用VLP-PCSK9肽疫苗，特别是PCSK9Qβ-003疫苗接种的小鼠产生了针对PCSK9的高滴度IgG抗体。PCSK9Qβ-003疫苗可明显降低Balb / c小鼠和LDLR的血浆总胆固醇^+/-小鼠。另外，PCSK9Qβ-003疫苗可降低血浆PCSK9水平并上调肝脏中的LDLR表达。此外，注射PCSK9Qβ-003疫苗与固醇调节元件结合蛋白2（SREBP-2），肝细胞核因子1α（HNF-1α）和3-羟基-3-甲基戊二酰辅酶A的显着上调有关（HMG-CoA）还原酶在LDLR ^+/-小鼠中。在接种的动物中未检测到明显的免疫损伤。因此，PCSK9Qβ-003疫苗可能通过降低胆固醇和调节脂质稳态来治疗高胆固醇血症。