Novel Intranasal vaccine composition of micellar lipid/peptide nanoparticles against the development of atherosclerotic and fatty liver disease.
For years now, the search for new and useful alternative pharmacological interventions in the prevention of atherosclerosis and its associated complications has taken place with limited success. The present study presents a novel vaccine composition of micellar lipid/peptide nanoparticles to be administered intranasally to prevent the process of atherogenesis and associated pathologies such as fatty liver development. Peptides employed correspond to the carboxy-end sequence of the cholesteryl-ester transfer protein (CETP), importantly implicated in atherogenesis (Biochem. Biophys. Res. Commun. 434:54-59, 2013; J. Struct. Biol. 186:19-27, 2014). The novelty of the vaccine compound of the present study includes the use of membrane lipids isolated from the archaebacteria Thermus acuaticus and lysophospholipids, which give peptides their adequate secondary structural conformation, paramount for autoimmune activity.
The vaccine composition has been shown to be useful raising an autoimmune response against CETP and therefore increasing HDL and lowering LDL-cholesterol plasma concentrations in two experimental animal models. The preclinical IFC study carried out in rabbits and the Barcelona study performed with pigs have shown that vaccination prevents the formation of plaque and vascular lesion in the aorta and drastically reduces the development of fibrosis and fatty liver in animals long term fed with a high cholesterol diet. The successful disease-preventive results obtained with our non-invasive intranasal vaccine composition during the preclinical stages of our study, has allowed us to advance and begin with clinical trials phase 1 and phase 2 in humans starting on the winter of 2015. Patent coverage: EP 1242446 B1; US 7749721 B2; MX 246945; PCT/MX2013/00078. Funding support: Conacyt grants 083673; 0141588; 0219327. Hamol Biosolutions development grant HB08.
Schematic representation of current knowledge of biochemical processes and immune activation involved in the development of atherosclerosis.