Vaccine-induced antibodies inhibit CETP activity in vivo and reduce aortic lesions in a rabbit model of atherosclerosis.
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.
Rittershaus
C W
CW
AVANT Immunotherapeutics, Inc, Needham, MA 02494, USA. crittershaus@avantimmune.com
Miller
D P
DP
Thomas
L J
LJ
Picard
M D
MD
Honan
C M
CM
Emmett
C D
CD
Pettey
C L
CL
Adari
H
H
Hammond
R A
RA
Beattie
D T
DT
Callow
A D
AD
Marsh
H C
HC
Ryan
U S
US
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*
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