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MF59-adjuvanted CETP vaccine protects rabbits from atherosclerosis without a strong antibody or CETP-activity effect (Iran J Basic Med Sci 2016)

Original title: A novel atheroprotective role of MF59-like adjuvant when co-administered with CETP vaccine in rabbit model of atherosclerosis

Iran J Basic Med Sci · · 5

Aghebati T, Mohammadpour AH, Afshar M, Jaafari MR, Abnous K, Nazemi S, Issazadeh S, Hashemzadeh S, Zare M, Badiee A

Researchers tested, for the first time, an MF59-like adjuvant for a tetanus-toxoid CETP peptide vaccine in a rabbit model of atherosclerosis, comparing it against the previously validated Alum/CpG formulation. Alum/CpG produced significantly more anti-CETP antibody than buffer (P less than 0.001), but MF59-like antibody induction was not significantly higher than buffer, and CETP activity and lipoprotein levels did not differ significantly between vaccinated and control rabbits in either group. Despite this, aortic atherosclerosis thickness grade was dramatically lower than buffer (P less than 0.01) in both vaccinated groups. The authors conclude the MF59-adjuvanted vaccine shows anti-atherosclerotic properties that cannot be directly attributed to the anti-CETP antibody response or CETP inhibition, warranting further mechanistic study.

Read the paper (DOI)PubMed

Original abstract

Objectives: 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.

Materials And 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.

Conclusion: 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.

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Summary written by cetpinhibition.org from the published abstract; figures as published. Page updated 19 August 2026. Methods.