Heart disease could eventually become as rare as polio or measles is today. Vaccinations eradicated these childhood illnesses decades ago. Now doctors are hoping a vaccine can be developed to prevent heart attacks and strokes."This is a very novel concept," said Dr. Prediman Krishan Shah, who is director of the Atherosclerosis Research Center at Cedars-Sinai Medical Center in Los Angeles. "Usually vaccines are to protect against infections, this is not protection against infection; it’s actually protecting the arteries from the buildup of LDL cholesterol," he said.
Cholesterol is believed to be an initiating factor of plaque buildup along the walls of the arteries. When arterial walls thicken from accumulation of plaque, arteries become narrowed, restricting blood flow, which is known as atherosclerosis. The end result can be a heart attack or stroke.
Shah has been conducting research on an atherosclerosis vaccine with a Swedish colleague, Dr. Jan Nilsson. Some research suggests that the immune system plays a dual role in atherosclerosis—that of arterial plaque formation, as well as artery protection.
"We began to look at this concept, whether the immune system could actually be utilized to reduce the amount of plaque buildup beginning with work in animal models," said Shah.
They started by isolating LDL cholesterol or "bad cholesterol," from the blood of rabbits and used it to make an LDL vaccine. The vaccine was tested on a genetically modified group of rabbits with high cholesterol. After several months of being fed a high fat diet, the immunized rabbits showed a 30 percent reduction in plaque buildup in their arteries.
"The challenge was how do we translate this work into something practical and useable in humans," said Shah.
Since it would not be practical to remove human blood and extract LDL cholesterol, Shah and Nilsson set out to find the specific part of the LDL molecule that is the antigen—the portion that triggers an immune response and the reduction of cholesterol in the arteries. They took the protein portion of LDL, called ApoB-100, and designed synthetic replicas of smaller portions of the protein called peptides. They tested these strands of peptides in human blood and found that it contained antibodies to several of the peptides, which meant that ApoB-100 must contain the antigen to LDL cholesterol.
The next step was to create vaccines using these peptides and test them in mice with high cholesterol and a propensity for extensive plaque buildup in their arteries. The researchers identified about three sequences of peptides, that when used in a vaccine, reduced plaque buildup by 65 to 75 percent in mice. The results of this research were published in the May 2003 issue of the Journal Arterial Thrombosis Vascular Biology.
In it they write "Our studies demonstrate the possibility of inhibiting development of atherosclerosis by activation of [artery protecting] immune responses against ApoB-100 peptide sequences."
Shah says he hopes that in the next two to four years they will have established the safety of an atherosclerosis vaccine in animals, and will be ready to test it in humans.
"Initially we will test the vaccine in humans with known vascular disease," said Shah, "but really the ultimate goal is, assuming it works in humans, to eventually explore the concept of using it as a childhood vaccine."
Since heart disease and plaque buildup start early in life, Shah says the childhood years are the ideal time to vaccinate in order to prevent heart attacks and strokes as adults.
While the vaccine appeared to be effective at reducing cholesterol in mice, Shah says they aren’t exactly sure how the vaccine works. They are currently running lab tests to determine if the vaccine provokes antibodies in the blood, if it mobilizes immune cells to attack and destroy cholesterol, or if it’s a combination of both.
And while the concept of a vaccine offers great hope to doctors who treat the millions of Americans with coronary artery disease, Dr. Shah does not expect it to be a cure-all.
"It’s going to be a complimentary approach, because Mother Nature is much harder to beat," he said, "this would not be a reason to abandon the proven methods of reducing risk—which are lifestyle modification and medication."
