期刊
VACCINE
卷 33, 期 43, 页码 5747-5755出版社
ELSEVIER SCI LTD
DOI: 10.1016/j.vaccine.2015.09.044
关键词
PCSK9; Vaccine; Virus-like particles; LDL Cholesterol
资金
- NIH [R01 AI083305]
- Intramural Research Program of NHLBI
- University of New Mexico Biology of Infectious Diseases and Inflammation Training Grant [T32 AI007538]
Proprotein convertase subtilisin/kexin type 9 (PCSK9) is a secretory protein that controls cholesterol homeostasis by enhancing endosomal and lysosomal degradation of the low-density lipoprotein receptor (LDL-R). Mutations that cause increased activity of PCSK9 are associated with hypercholesterolemia, atherosclerosis and early cardiovascular disease (CVD), whereas individuals with loss-of-function mutations in PCSK9 are apparently healthy but are hypocholesterolemic and have a dramatically decreased risk of CVD. In this study, we generated virus-like particle (VLP)-based vaccines targeting PCSK9. Mice and macaques vaccinated with bacteriophage VLPs displaying PCSK9-derived peptides developed high titer IgG antibodies that bound to circulating PCSK9. Vaccination was associated with significant reductions in total cholesterol, free cholesterol, phospholipids, and triglycerides. A vaccine targeting PCSK9 may, therefore, be an attractive alternative to monoclonal antibody-based therapies. (C) 2015 Elsevier Ltd. All rights reserved.
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