a novel atheroprotective role of mf59-like adjuvant when co-administered with cetp vaccine in rabbit model of atherosclerosis
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abstract
objective(s): 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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Journal title:
iranian journal of basic medical sciencesجلد ۱۹، شماره ۱۲، صفحات ۱۳۴۵-۱۳۵۲
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