A cholesterol-lowering VLP vaccine that targets PCSK9.
Vaccine
; 33(43): 5747-5755, 2015 Oct 26.
Article
en En
| MEDLINE
| ID: mdl-26413878
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.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Colesterol
/
Proproteína Convertasas
/
Vacunas de Partículas Similares a Virus
Límite:
Animals
Idioma:
En
Revista:
Vaccine
Año:
2015
Tipo del documento:
Article
País de afiliación:
Estados Unidos