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  • Title: A Therapeutic Peptide Vaccine Against PCSK9.
    Author: Pan Y, Zhou Y, Wu H, Chen X, Hu X, Zhang H, Zhou Z, Qiu Z, Liao Y.
    Journal: Sci Rep; 2017 Oct 02; 7(1):12534. PubMed ID: 28970592.
    Abstract:
    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.
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