The safety and immunogenicity of a CETP vaccine in healthy adults.
A cholesterol ester transfer protein (CETP) vaccine (CETi-1) that induces auto-antibodies that specifically bind and inhibit activity of endogenous CETP has been demonstrated in rabbits to significantly increase HDL-C and reduce the development of atherosclerosis. In a Phase I human trial with CETi-1, one patient at the highest dose (250 mg) out of a total of 36 patients who received a single injection developed anti-CETP antibodies. In an extension study of 23 patients, 53% (8/15) who received a second injection of the active vaccine developed anti-CETP antibodies compared with 0% (0/8) in the placebo group. The vaccine was well tolerated and no significant laboratory abnormalities occurred. CETi-1 is a feasible therapy in humans to induce CETP auto-antibodies. Future research will determine if repeat inoculations will induce a sufficient anti-CETP antibody response to inhibit CETP and increase HDL levels.
Davidson
Michael H
MH
Rush-Presbyterian-St Luke's Medical Center, Chicago Center for Clinical Research, 515 North State Street, Suite 2700, Chicago, IL 60610, USA. mdavidson@protocare.com
Maki
Kevin
K
Umporowicz
Denise
D
Wheeler
Alistair
A
Rittershaus
Charles
C
Ryan
Una
U
D001323:Autoantibodies / Q000096:biosynthesis*; D002352:Carrier Proteins / Q000276:immunology*; D053480:Cholesterol Ester Transfer Proteins; D002788:Cholesterol Esters / Q000276:immunology*; D008076:Cholesterol, HDL / Q000097:blood; D004306:Dose-Response Relationship, Immunologic; D004311:Double-Blind Method; D006023:Glycoproteins; D006801:Humans; D014614:Vaccines, Synthetic / Q000009:adverse effects / Q000276:immunology*
D001323:Autoantibodies; C506642:CETP protein, human; D002352:Carrier Proteins; D053480:Cholesterol Ester Transfer Proteins; D002788:Cholesterol Esters; D008076:Cholesterol, HDL; D006023:Glycoproteins; D014614:Vaccines, Synthetic