| First Author | Pan Y | Year | 2017 |
| Journal | Sci Rep | Volume | 7 |
| Issue | 1 | Pages | 12534 |
| PubMed ID | 28970592 | Mgi Jnum | J:255760 |
| Mgi Id | MGI:6109861 | Doi | 10.1038/s41598-017-13069-w |
| Citation | Pan Y, et al. (2017) A Therapeutic Peptide Vaccine Against PCSK9. Sci Rep 7(1):12534 |
| abstractText | 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 PCSK9Qbeta-003 vaccine, developed high titer IgG antibodies against PCSK9. PCSK9Qbeta-003 vaccine obviously decreased plasma total cholesterol in both Balb/c mice and LDLR(+/-) mice. Also, PCSK9Qbeta-003 vaccine decreased plasma PCSK9 level and up-regulated LDLR expression in liver. Additionally, PCSK9Qbeta-003 vaccine injection was associated with significant up-regulation of sterol-regulatory element-binding protein-2 (SREBP-2), hepatocyte nuclear factor 1alpha (HNF-1alpha), and 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase in LDLR(+/-) mice. No obvious immune injury was detected in vaccinated animals. The PCSK9Qbeta-003 vaccine, therefore, may be an attractive treatment approach for hypercholesterolemia through decreasing cholesterol and regulating lipid homeostasis. |
