Cargando…
A virus-like particle-based bivalent PCSK9 vaccine lowers LDL-cholesterol levels in non-human primates
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 f...
Autores principales: | , , , , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2023
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10539315/ https://www.ncbi.nlm.nih.gov/pubmed/37770440 http://dx.doi.org/10.1038/s41541-023-00743-6 |
_version_ | 1785113471225954304 |
---|---|
author | Fowler, Alexandra Van Rompay, Koen K. A. Sampson, Maureen Leo, Javier Watanabe, Jennifer K. Usachenko, Jodie L. Immareddy, Ramya Lovato, Debbie M. Schiller, John T. Remaley, Alan T. Chackerian, Bryce |
author_facet | Fowler, Alexandra Van Rompay, Koen K. A. Sampson, Maureen Leo, Javier Watanabe, Jennifer K. Usachenko, Jodie L. Immareddy, Ramya Lovato, Debbie M. Schiller, John T. Remaley, Alan T. Chackerian, Bryce |
author_sort | Fowler, Alexandra |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-10539315 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-105393152023-09-30 A virus-like particle-based bivalent PCSK9 vaccine lowers LDL-cholesterol levels in non-human primates Fowler, Alexandra Van Rompay, Koen K. A. Sampson, Maureen Leo, Javier Watanabe, Jennifer K. Usachenko, Jodie L. Immareddy, Ramya Lovato, Debbie M. Schiller, John T. Remaley, Alan T. Chackerian, Bryce NPJ Vaccines Article 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. Nature Publishing Group UK 2023-09-28 /pmc/articles/PMC10539315/ /pubmed/37770440 http://dx.doi.org/10.1038/s41541-023-00743-6 Text en © The Author(s) 2023 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . |
spellingShingle | Article Fowler, Alexandra Van Rompay, Koen K. A. Sampson, Maureen Leo, Javier Watanabe, Jennifer K. Usachenko, Jodie L. Immareddy, Ramya Lovato, Debbie M. Schiller, John T. Remaley, Alan T. Chackerian, Bryce A virus-like particle-based bivalent PCSK9 vaccine lowers LDL-cholesterol levels in non-human primates |
title | A virus-like particle-based bivalent PCSK9 vaccine lowers LDL-cholesterol levels in non-human primates |
title_full | A virus-like particle-based bivalent PCSK9 vaccine lowers LDL-cholesterol levels in non-human primates |
title_fullStr | A virus-like particle-based bivalent PCSK9 vaccine lowers LDL-cholesterol levels in non-human primates |
title_full_unstemmed | A virus-like particle-based bivalent PCSK9 vaccine lowers LDL-cholesterol levels in non-human primates |
title_short | A virus-like particle-based bivalent PCSK9 vaccine lowers LDL-cholesterol levels in non-human primates |
title_sort | virus-like particle-based bivalent pcsk9 vaccine lowers ldl-cholesterol levels in non-human primates |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10539315/ https://www.ncbi.nlm.nih.gov/pubmed/37770440 http://dx.doi.org/10.1038/s41541-023-00743-6 |
work_keys_str_mv | AT fowleralexandra aviruslikeparticlebasedbivalentpcsk9vaccinelowersldlcholesterollevelsinnonhumanprimates AT vanrompaykoenka aviruslikeparticlebasedbivalentpcsk9vaccinelowersldlcholesterollevelsinnonhumanprimates AT sampsonmaureen aviruslikeparticlebasedbivalentpcsk9vaccinelowersldlcholesterollevelsinnonhumanprimates AT leojavier aviruslikeparticlebasedbivalentpcsk9vaccinelowersldlcholesterollevelsinnonhumanprimates AT watanabejenniferk aviruslikeparticlebasedbivalentpcsk9vaccinelowersldlcholesterollevelsinnonhumanprimates AT usachenkojodiel aviruslikeparticlebasedbivalentpcsk9vaccinelowersldlcholesterollevelsinnonhumanprimates AT immareddyramya aviruslikeparticlebasedbivalentpcsk9vaccinelowersldlcholesterollevelsinnonhumanprimates AT lovatodebbiem aviruslikeparticlebasedbivalentpcsk9vaccinelowersldlcholesterollevelsinnonhumanprimates AT schillerjohnt aviruslikeparticlebasedbivalentpcsk9vaccinelowersldlcholesterollevelsinnonhumanprimates AT remaleyalant aviruslikeparticlebasedbivalentpcsk9vaccinelowersldlcholesterollevelsinnonhumanprimates AT chackerianbryce aviruslikeparticlebasedbivalentpcsk9vaccinelowersldlcholesterollevelsinnonhumanprimates AT fowleralexandra viruslikeparticlebasedbivalentpcsk9vaccinelowersldlcholesterollevelsinnonhumanprimates AT vanrompaykoenka viruslikeparticlebasedbivalentpcsk9vaccinelowersldlcholesterollevelsinnonhumanprimates AT sampsonmaureen viruslikeparticlebasedbivalentpcsk9vaccinelowersldlcholesterollevelsinnonhumanprimates AT leojavier viruslikeparticlebasedbivalentpcsk9vaccinelowersldlcholesterollevelsinnonhumanprimates AT watanabejenniferk viruslikeparticlebasedbivalentpcsk9vaccinelowersldlcholesterollevelsinnonhumanprimates AT usachenkojodiel viruslikeparticlebasedbivalentpcsk9vaccinelowersldlcholesterollevelsinnonhumanprimates AT immareddyramya viruslikeparticlebasedbivalentpcsk9vaccinelowersldlcholesterollevelsinnonhumanprimates AT lovatodebbiem viruslikeparticlebasedbivalentpcsk9vaccinelowersldlcholesterollevelsinnonhumanprimates AT schillerjohnt viruslikeparticlebasedbivalentpcsk9vaccinelowersldlcholesterollevelsinnonhumanprimates AT remaleyalant viruslikeparticlebasedbivalentpcsk9vaccinelowersldlcholesterollevelsinnonhumanprimates AT chackerianbryce viruslikeparticlebasedbivalentpcsk9vaccinelowersldlcholesterollevelsinnonhumanprimates |