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Production of Apolipoprotein C-III Knockout Rabbits using Zinc Finger Nucleases

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Vaccine-induced antibodies inhibit CETP activity in vivo and reduce aortic lesions in a rabbit model of

C W Rittershaus¹, D P Miller, L J Thomas

¹AVANT Immunotherapeutics, Inc, Needham, MA 02494, USA. crittershaus@avantimmune.com

Arteriosclerosis, Thrombosis, and Vascular Biology

|September 9, 2000

Summary

Vaccinating rabbits against cholesteryl ester transfer protein (CETP) reduced CETP activity and atherosclerosis. This suggests that inhibiting CETP via vaccination is a viable strategy for managing cardiovascular disease.

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Area of Science:

Cardiovascular Science
Immunology
Lipid Metabolism

Background:

Cholesteryl ester transfer protein (CETP) plays a key role in lipoprotein metabolism.
Inhibition of CETP is a potential therapeutic target for atherosclerosis.
Vaccination strategies against self-antigens are being explored for disease management.

Purpose of the Study:

To investigate the efficacy of a vaccine targeting cholesteryl ester transfer protein (CETP) in reducing CETP activity and mitigating atherosclerosis.
To evaluate the impact of CETP inhibition on lipoprotein profiles and atherosclerotic lesion development in a rabbit model.

Main Methods:

New Zealand White rabbits were immunized with a peptide containing a functional region of CETP.
Plasma CETP activity, lipoprotein profiles (HDL, LDL cholesterol fractions), and atherosclerotic lesion size in the aorta were measured.
A cholesterol-fed rabbit model was used to induce atherosclerosis.

Main Results:

CETP-vaccinated rabbits showed significantly reduced plasma CETP activity compared to controls.
Vaccination led to a higher fraction of plasma cholesterol in HDL (42% increase) and a lower fraction in LDL (24% decrease).
Atherosclerotic lesions in the aorta were reduced by 39.6% in the CETP-vaccinated group.

Conclusions:

Vaccination with a CETP-derived peptide effectively reduces CETP activity in vivo.
Inhibition of CETP activity through vaccination demonstrates antiatherogenic effects.
Vaccination against self-antigens represents a promising therapeutic approach for disease management, including atherosclerosis.