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Liposomal CETP vaccine protects rabbits against atherosclerosis where the failed clinical peptide vaccine did not (Pharm Dev Technol 2019)

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

Pharm Dev Technol · · 6

Aghebati T, Arabsalmani M, Mohammadpour AH, Afshar M, Jaafari MR, Abnous K, Nazemi S, Badiee A

Earlier clinical trials of a CETP peptide vaccine were stopped after disappointing results, attributed to aluminium hydroxide adjuvant inadequately stimulating an immune response against the self-antigen. Researchers developed a novel liposomal tetanus-toxoid-CETP peptide vaccine (Lip-CETP) and tested it in cholesterol-fed rabbits, comparing Lip-CETP alone, Lip-CETP with CpG adjuvant, and controls. Lip-CETP with CpG elicited strong anti-TT-CETP antibodies and a higher interferon-gamma level than buffer controls. Plasma lipoproteins did not differ significantly between groups, but aortic atherosclerosis thickness was significantly lower than controls (P less than 0.001) in rabbits vaccinated with Lip-CETP alone, though not with the CpG-adjuvanted version, demonstrating a strong atheroprotective effect for this liposomal formulation.

Read the paper (DOI)PubMed

Original 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.

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