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A Single‐Dose, Implant‐Based, Trivalent Virus‐like Particle Vaccine against “Cholesterol Checkpoint” Proteins
Author(s) -
OrtegaRivera Oscar A.,
Pokorski Jonathan K.,
Steinmetz Nicole F.
Publication year - 2021
Publication title -
advanced therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.125
0ISSN - 2366-3987
DOI - 10.1002/adtp.202100014
Subject(s) - cholesterol , proprotein convertase , kexin , apolipoprotein b , vaccination , chemistry , lipoprotein , virology , medicine , biochemistry , ldl receptor
Cardiovascular disease is the number one cause of death globally. Lowering cholesterol levels in plasma is the mainstay therapy; however lifelong treatment and adverse effects call for improved therapeutic interventions. A trivalent vaccine candidate targeting proprotein convertase subtilisin/kexin‐9 (PCSK9), apolipoprotein B (ApoB), and cholesteryl ester transfer protein (CETP) is developed. Vaccine candidates are developed using bacteriophage Qβ‐based virus‐like particles (VLPs) displaying antigens of PCKS9, ApoB, and CETP, respectively. Vaccine candidate mixtures are formulated as slow‐release PLGA:VLP implants using hot‐melt extrusion. The delivery of the trivalent vaccine candidate via the implant produced antibodies against the cholesterol checkpoint proteins at levels comparable to a three‐dose injection schedule with soluble mixtures. The reduction in PCSK9 and ApoB levels in plasma, inhibition of CETP (in vitro), and total plasma cholesterol decrease is achieved. Altogether, a platform technology for a single‐dose multi‐agent proteins is presented.