title: Vaccine-induced antibodies inhibit CETP activity in vivo and reduce aortic lesions in a rabbit model of atherosclerosis.
abstract: Using a vaccine approach, we immunized New Zealand White rabbits with a peptide containing a region of cholesteryl ester transfer protein (CETP) known to be required for neutral lipid transfer function. These rabbits had significantly reduced plasma CETP activity and an altered lipoprotein profile. In a cholesterol-fed rabbit model of atherosclerosis, the fraction of plasma cholesterol in HDL was 42% higher and the fraction of plasma cholesterol in LDL was 24% lower in the CETP-vaccinated group than in the control-vaccinated group. Moreover, the percentage of the aorta surface exhibiting atherosclerotic lesion was 39.6% smaller in the CETP-vaccinated rabbits than in controls. The data reported here demonstrate that CETP activity can be reduced in vivo by vaccination with a peptide derived from CETP and support the concept that inhibition of CETP activity in vivo can be antiatherogenic. In addition, these studies suggest that vaccination against a self-antigen is a viable therapeutic strategy for disease management.
authors.affiliation: AVANT Immunotherapeutics, Inc, Needham, MA 02494, USA. crittershaus@avantimmune.com
authors.forename: C W
authors.initials: CW
authors.lastname: Rittershaus
authors.forename: D P
authors.initials: DP
authors.lastname: Miller
authors.forename: L J
authors.initials: LJ
authors.lastname: Thomas
authors.forename: M D
authors.initials: MD
authors.lastname: Picard
authors.forename: C M
authors.initials: CM
authors.lastname: Honan
authors.forename: C D
authors.initials: CD
authors.lastname: Emmett
authors.forename: C L
authors.initials: CL
authors.lastname: Pettey
authors.forename: H
authors.initials: H
authors.lastname: Adari
authors.forename: R A
authors.initials: RA
authors.lastname: Hammond
authors.forename: D T
authors.initials: DT
authors.lastname: Beattie
authors.forename: A D
authors.initials: AD
authors.lastname: Callow
authors.forename: H C
authors.initials: HC
authors.lastname: Marsh
authors.forename: U S
authors.initials: US
authors.lastname: Ryan
mesh_terms: D000818:Animals; D000906:Antibodies / Q000097:blood; D001011:Aorta / Q000473:pathology*; D001161:Arteriosclerosis / Q000276:immunology / Q000378:metabolism* / Q000473:pathology / Q000628:therapy; D015153:Blotting, Western; D016466:CHO Cells; D002352:Carrier Proteins / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D053480:Cholesterol Ester Transfer Proteins; D002791:Cholesterol, Dietary / Q000494:pharmacology; D006224:Cricetinae; D004195:Disease Models, Animal; D006023:Glycoproteins; D006801:Humans; D007677:Kidney Function Tests; D008074:Lipoproteins / Q000032:analysis; D011817:Rabbits; D011994:Recombinant Proteins / Q000276:immunology / Q000378:metabolism; D014614:Vaccines, Synthetic / Q000008:administration & dosage / Q000276:immunology*
chemical_list: D000906:Antibodies; C506642:CETP protein, human; D002352:Carrier Proteins; D053480:Cholesterol Ester Transfer Proteins; D002791:Cholesterol, Dietary; D006023:Glycoproteins; D008074:Lipoproteins; D011994:Recombinant Proteins; D014614:Vaccines, Synthetic