Abstract 11020: Affitope®-Based Anti-PCSK9 Vaccines
Background: Proprotein Convertase Subtilisin/Kexin type 9 (PCSK9) modulates the circulating Low Density Lipoprotein cholesterol (LDLc) concentrations by binding and subsequently promoting the degradation of the Low Density Lipoprotein Receptor (LDLR). Many studies confirmed the beneficial effect on LDLc by inhibiting the PCSK9/LDLR interaction, which highlighted PCSK9 as a potential and very attractive target for the LDLc management. To date, the most advance approaches for inhibiting the PCSK9 action on LDLR are monoclonal antibody (mAb) therapies. However, because of their relatively short in vivo half-life time, mAb face functional limitations. Hence, long term efficacy of mAb treatments is linked to frequent treatments and high costs.
Aim: Development of a PCSK9 peptide-based active immunotherapy resulting in sustained lower LDLc.
Methods: AFFITOPEs® (antigenic peptides) that induce PCSK9 specific antibody response have been selected by using the proprietary AFFITOME® technology. The AFFITOPE® vaccine candidates were coupled to a carrier-protein and together with an adjuvant administered subcutaneously in mice and rats. In addition, PCSK9 specific antibodies were used for comparison. Concentration and efficacy of AFFITOPE®-induced autologous antibodies or passively administered antibodies are monitored by anti-PCSK9 protein ELISA. Moreover, target engagement, plasma cholesterol concentration, lipoprotein profile (VLDL, LDL, HDL) and liver LDLR levels are determined in both groups.
Results: AFFITOPE®-based anti-PCSK9 vaccines induce persistent, functional antibodies which reduce plasma cholesterol levels for up to one year.
Conclusions: AFFITOPE®-based PCSK9 vaccines are an innovative approach and a powerful strategy for the long term management of LDLc levels.
- © 2013 by American Heart Association, Inc.