Abstract 15205: Atheroprotective Effect of the AFFITOPE®-based Anti-PCSK9 Vaccine (AT04A) in APOE*3Leiden.CETP Mice

Background: Elevated low density lipoprotein cholesterol (LDLc) is one of the major risk factors for premature cardiovascular diseases (CVD). Thus, therapeutic approaches aim at reducing LDLc. PCSK9 (Proprotein Convertase Subtilisin/Kexin type 9) has been shown to be a key regulator of the LDLR-mediated cholesterol clearance pathway. Many preclinical and clinical studies confirm the LDLc-lowering effect of PCSK9 inhibition, and emphasize PCSK9 as a potential novel target for the treatment of CVD. Aim: Proof of concept study for AFFITOPE®-based (AT04A) anti-PCSK9 immunization in the APOE*3Leiden.CETP mouse model and its safety aspects. Methods: AT04A vaccine was administered subcutaneously in APOE*3Leiden.CETP mice. Control and vaccine treated mice were fed Western-type diet for 18 weeks. Antibody titers and concentration, and their affinity towards PCSK9, as well as plasma lipids were monitored throughout the whole study by ELISA, Biacore® and FPLC, respectively. Moreover, body weight (BW), food intake (F...