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Vaccine. 2015 Oct 26;33(43):5747-55. doi: 10.1016/j.vaccine.2015.09.044. Epub 2015 Sep 26.

A cholesterol-lowering VLP vaccine that targets PCSK9.

Author information

  • 1Department of Molecular Genetics and Microbiology, University of New Mexico, MSC08-4660, Albuquerque, NM 87131, USA.
  • 2Lipoprotein Metabolism Section, Cardio-Pulmonary Branch, National Heart, Lung and Blood Institute, National Institutes of Health, Building 10 - 2C433, 10 Center Drive, MSC 1666, Bethesda, MD 20892, USA.
  • 3Laboratory of Cellular Oncology, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.
  • 4Department of Molecular Genetics and Microbiology, University of New Mexico, MSC08-4660, Albuquerque, NM 87131, USA. Electronic address: bchackerian@salud.unm.edu.
  • 5Lipoprotein Metabolism Section, Cardio-Pulmonary Branch, National Heart, Lung and Blood Institute, National Institutes of Health, Building 10 - 2C433, 10 Center Drive, MSC 1666, Bethesda, MD 20892, USA. Electronic address: aremaley1@nhlbi.nih.gov.

Abstract

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.

Copyright © 2015 Elsevier Ltd. All rights reserved.

KEYWORDS:

LDL Cholesterol; PCSK9; Vaccine; Virus-like particles

PMID:
26413878
[PubMed - in process]
PMCID:
PMC4609631
[Available on 2016-10-26]
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