A virus-like particle-based bivalent PCSK9 vaccine lowers LDL-cholesterol levels in non-human primates.
Journal
NPJ vaccines
ISSN: 2059-0105
Titre abrégé: NPJ Vaccines
Pays: England
ID NLM: 101699863
Informations de publication
Date de publication:
28 Sep 2023
28 Sep 2023
Historique:
received:
15
05
2023
accepted:
15
09
2023
medline:
29
9
2023
pubmed:
29
9
2023
entrez:
28
9
2023
Statut:
epublish
Résumé
Elevated low-density lipoprotein cholesterol (LDL-C) is an important risk factor in the development of atherosclerotic cardiovascular disease (ASCVD). Inhibitors of proprotein convertase subtilisin/kexin type 9 (PCSK9), a negative regulator of LDL-C metabolism, have emerged as promising approaches for reducing elevated LDL-C levels. Here, we evaluated the cholesterol-lowering efficacy of virus-like particle (VLP) based vaccines that target epitopes found within the LDL receptor (LDL-R) binding domain of PCSK9. In both mice and non-human primates, a bivalent VLP vaccine targeting two distinct epitopes on PCSK9 elicited strong and durable antibody responses and lowered cholesterol levels. In macaques, a VLP vaccine targeting a single PCSK9 epitope was only effective at lowering LDL-C levels in combination with statins, whereas immunization with the bivalent vaccine lowered LDL-C without requiring statin co-administration. These data highlight the efficacy of an alternative, vaccine-based approach for lowering LDL-C.
Identifiants
pubmed: 37770440
doi: 10.1038/s41541-023-00743-6
pii: 10.1038/s41541-023-00743-6
pmc: PMC10539315
doi:
Types de publication
Journal Article
Langues
eng
Pagination
142Subventions
Organisme : NHLBI NIH HHS
ID : R01 HL131696
Pays : United States
Organisme : NIH HHS
ID : P51 OD011107
Pays : United States
Organisme : NCATS NIH HHS
ID : UL1 TR001449
Pays : United States
Commentaires et corrections
Type : UpdateOf
Informations de copyright
© 2023. Springer Nature Limited.
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