Long-term generation of antiPCSK9 antibody using a nanoliposome-based vaccine delivery system

Atherosclerosis
Amir Abbas Momtazi-BorojeniAmirhossein Sahebkar

Abstract

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+). To evaluate induction of antiPCSK9 antibody in vivo, BALB/c mice were subcutaneou...Continue Reading

Citations

Jun 28, 2019·Current Opinion in Cardiology·Tahir Mahmood, Michael D Shapiro
Sep 2, 2020·Biochemical Society Transactions·Klaus Ley
Aug 2, 2020·Cardiology and Therapy·Stefan TothJan Fedacko
Jun 27, 2019·High Blood Pressure & Cardiovascular Prevention : the Official Journal of the Italian Society of Hypertension·Rita Del PintoClaudio Ferri
Sep 14, 2020·The Korean Journal of Internal Medicine·Kyung Hoon Cho, Young Joon Hong
Jun 27, 2019·European Heart Journal. Cardiovascular Pharmacotherapy·Amir Abbas Momtazi-BorojeniAmirhossein Sahebkar
Dec 11, 2019·BMC Medicine·Amir Abbas Momtazi-BorojeniAmirhossein Sahebkar
Jan 12, 2021·Advanced Drug Delivery Reviews·Jun ChenHo-Wook Jun
Jun 1, 2021·Biomedicine & Pharmacotherapy = Biomédecine & Pharmacothérapie·Khadijeh MahboobniaAmirhossein Sahebkar
Jun 19, 2021·Biochimica Et Biophysica Acta. Reviews on Cancer·Anindita BhattacharyaPraphulla Chandra Shukla
Jun 22, 2021·European Heart Journal·Amirhossein SahebkarMaciej Banach
Aug 7, 2021·Vaccines·Amir Abbas Momtazi-BorojeniAmirhossein Sahebkar
May 24, 2020·Atherosclerosis·Johan G SchnitzlerJeffrey Kroon

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