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Research Articles

Development of an effective liposomal cholesterol ester transfer protein (CETP) vaccine for protecting against atherosclerosis in rabbit model

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Pages 432-439 | Received 02 Oct 2019, Accepted 14 Dec 2019, Published online: 26 Dec 2019
 

Abstract

Clinical trials of cholesterol ester transfer protein (CETP) peptide vaccine were stopped after disappointing results in humans due to the inadequacy of adjuvant aluminum hydroxide in stimulating the immune response against the self-antigen of CETP. To increase the efficacy of the CETP vaccine, we developed a novel liposomal form of tetanus toxoid-CETP (TT-CETP) peptide (Lip CETP) with well-characterized properties and high encapsulation efficiency. The vaccine efficacy against atherosclerosis was evaluated in rabbits challenged with a high cholesterol diet. Rabbits were immunized with Lip-CETP or liposome containing CETP with CpG ODN (Lip CETP/CpG). Control groups received empty liposomes or buffer. Anti-TT-CETP specific antibodies in serum were determined and gene expression of cytokine IFN-γ and IL-4 were measured in blood peripheral mononuclear cells. Therapeutic response was evaluated by titration of plasma lipoproteins during the study and pathologic analysis of aorta atherosclerotic lesions at the end. Lip-CETP/CpG elicited strong anti-TT-CETP antibodies and a higher IFN-γ level than the buffer. IL-4 was lower than the buffer in all vaccinated groups. Plasma lipoproteins showed no significant difference in the studied groups. Atherosclerosis thickness grade of the aorta was lower than the buffer group (p < 0.001) in rabbits vaccinated with Lip-CETP but not with Lip-CETP/CpG. In conclusion, Lip-CETP showed a strong atheroprotective effect.

Graphical Abstract

Acknowledgments

This study is a part of the PhD thesis of the first author Tamara Aghebati.

Disclosure statement

The authors declare that they have no conflict of interest.

Additional information

Funding

This research was supported by Vice Chancellor for Education and Research of Razavi Hospital (Mashhad, Iran) [940492].

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