title: A novel atheroprotective role of MF59-like adjuvant when co-administered with CETP vaccine in rabbit model of atherosclerosis.
abstract: OBJECTIVE
  In this study, for the first time, MF59 adjuvant was used to develop a cholesteryl ester transfer protein (CETP) vaccine. The efficacy of the vaccine was compared with the efficacy of CETP vaccine formulated with Alum/CpG, the formulation that its immunogenicity has been already demonstrated in rabbit and mice.
  
  
  METHODS
  Tetanus toxoid- CETP peptide (TT-CETP) was mixed with Alum/CpG or MF59-like and administered subcutaneously for total five times in rabbit model of atherosclerosis. Anti-TT-CETP specific antibody, CETP activity in sera and mRNA level of cytokine IL-4 and IFN-γ in peripheral mononuclear cells were determined. Therapeutic response was also examined by tracking serum lipoprotein levels and pathologic observation of atherosclerotic lesions at aortic site.
  
  
  RESULTS
  More anti-TT-CETP antibody was found in Alum/CpG vaccinated rabbits compared to buffer (P<0.001). Antibody induced by MF59-like formulation was not significantly higher than buffer. CETP activity and lipoprotein levels were not significantly different between vaccinated and control rabbits. The mRNA level of IL-4 was significantly lower than buffer while, IFN-γ gene expression was significantly higher in both vaccinated groups. Atherosclerosis thickness grade of aorta was dramatically lower than buffer (P<0.01) in both vaccinated groups.
  
  
  CONCLUSIONS
  It is concluded that MF59-adjuvanted CETP vaccine showed anti-atherosclerosis properties, but the protective effect could not be directly attributed to the immune response induced by anti TT-CETP antibody and CETP inhibition. Further studies are needed to explain the anti-atherosclerosis properties of MF59 in the presence of TT-CETP peptide.
authors.affiliation: Nanotechnology Research Center, Mashhad University of Medical Sciences, Mashhad, Iran.
authors.forename: Tamara
authors.initials: T
authors.lastname: Aghebati
authors.affiliation: Pharmaceutical Research Center, Mashhad University of Medical Sciences, Mashhad, Iran.
authors.forename: Amir Hooshang
authors.initials: AH
authors.lastname: Mohammadpour
authors.affiliation: Department of Anatomy, Faculty of Medicine, Birjand University of Medical Sciences, Birjand, Iran; Medical Toxicology Research Centre, Mashhad University of Medical Sciences, Mashhad, Iran.
authors.forename: Mohammad
authors.initials: M
authors.lastname: Afshar
authors.affiliation: Biotechnology Research Center, Mashhad University of Medical Sciences, Mashhad, Iran.
authors.forename: Mahmoud Reza
authors.initials: MR
authors.lastname: Jaafari
authors.affiliation: Pharmaceutical Research Center, Mashhad University of Medical Sciences, Mashhad, Iran.
authors.forename: Khalil
authors.initials: K
authors.lastname: Abnous
authors.affiliation: Research and Education Department, Razavi Hospital, Mashhad, Iran.
authors.forename: Saeed
authors.initials: S
authors.lastname: Nazemi
authors.affiliation: Research and Education Department, Razavi Hospital, Mashhad, Iran.
authors.forename: Sobhan
authors.initials: S
authors.lastname: Issazadeh
authors.affiliation: Research and Education Department, Razavi Hospital, Mashhad, Iran.
authors.forename: Saeed
authors.initials: S
authors.lastname: Hashemzadeh
authors.affiliation: Hefdahe Shahrivar Hospital, Mashhad, Iran.
authors.forename: Mohammad
authors.initials: M
authors.lastname: Zare
authors.affiliation: Nanotechnology Research Center, Mashhad University of Medical Sciences, Mashhad, Iran.
authors.forename: Ali
authors.initials: A
authors.lastname: Badiee
keywords: Alum/CpG; Atherosclerosis Cardiovascular disease; CETP vaccine; MF59