Long-term generation of antiPCSK9 antibody using a nanoliposome-based vaccine delivery system.
Animals
Antibodies
/ pharmacology
Cholesterol, LDL
/ drug effects
Disease Models, Animal
Drug Delivery Systems
Enzyme-Linked Immunosorbent Assay
Follow-Up Studies
Liposomes
Male
Mice
Mice, Inbred BALB C
Proprotein Convertase 9
/ immunology
Time Factors
Vaccination
/ methods
Vaccines, Subunit
/ pharmacology
Antibody
Antigen
Nanoliposome
PCSK9
Vaccine
Journal
Atherosclerosis
ISSN: 1879-1484
Titre abrégé: Atherosclerosis
Pays: Ireland
ID NLM: 0242543
Informations de publication
Date de publication:
04 2019
04 2019
Historique:
received:
13
11
2018
revised:
17
01
2019
accepted:
05
02
2019
pubmed:
25
2
2019
medline:
13
5
2020
entrez:
25
2
2019
Statut:
ppublish
Résumé
Proprotein convertase subtilisin kexin type 9 (PCSK9) is a liver secretory enzyme that controls plasma low-density lipoprotein cholesterol (LDL-C) levels through modulation of LDL receptor (LDLR). Inhibition of PCSK9 using monoclonal antibodies (mAbs) can efficiently lower plasma LDL-C. However, the relatively short half-life of mAbs necessitates frequent passive immunization, which is costly. These limitations can be circumvented by active immunization. Here, we evaluated the long-term antiPCSK9 antibody generation in BALB/c mice vaccinated with a nanoliposomal PCSK9-specific active vaccine. Negatively charged nanoliposomes were used as a vaccine delivery system and prepared via lipid-film hydration method. We constructed a peptide vaccine termed Immunogenic Fused PCSK9-Tetanus (IFPT) by linking a short PCSK9 peptide (as B cell epitope) to a tetanus peptide (as T cell epitope). The IFPT peptide was conjugated to the surface of nanoliposome carriers using a DSPE-PEG- Maleimide (1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[maleimide(PEG)-2000]) linker. Nanoliposomal IFPT (L-IFPT) construct was formulated with alum vaccine adjuvant (L-IFPTA The L-IFPTA The results indicate efficient activity of the tested nanoliposomal construct (L-IFPTA
Sections du résumé
BACKGROUND AND AIMS
Proprotein convertase subtilisin kexin type 9 (PCSK9) is a liver secretory enzyme that controls plasma low-density lipoprotein cholesterol (LDL-C) levels through modulation of LDL receptor (LDLR). Inhibition of PCSK9 using monoclonal antibodies (mAbs) can efficiently lower plasma LDL-C. However, the relatively short half-life of mAbs necessitates frequent passive immunization, which is costly. These limitations can be circumvented by active immunization. Here, we evaluated the long-term antiPCSK9 antibody generation in BALB/c mice vaccinated with a nanoliposomal PCSK9-specific active vaccine.
METHODS
Negatively charged nanoliposomes were used as a vaccine delivery system and prepared via lipid-film hydration method. We constructed a peptide vaccine termed Immunogenic Fused PCSK9-Tetanus (IFPT) by linking a short PCSK9 peptide (as B cell epitope) to a tetanus peptide (as T cell epitope). The IFPT peptide was conjugated to the surface of nanoliposome carriers using a DSPE-PEG- Maleimide (1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[maleimide(PEG)-2000]) linker. Nanoliposomal IFPT (L-IFPT) construct was formulated with alum vaccine adjuvant (L-IFPTA
RESULTS
The L-IFPTA
CONCLUSIONS
The results indicate efficient activity of the tested nanoliposomal construct (L-IFPTA
Identifiants
pubmed: 30797988
pii: S0021-9150(19)30063-2
doi: 10.1016/j.atherosclerosis.2019.02.001
pii:
doi:
Substances chimiques
Antibodies
0
Cholesterol, LDL
0
Liposomes
0
Vaccines, Subunit
0
Pcsk9 protein, mouse
EC 3.4.21.-
Proprotein Convertase 9
EC 3.4.21.-
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
69-78Informations de copyright
Copyright © 2019 Elsevier B.V. All rights reserved.