There’s a new vaccine to protect against high cholesterol and its consequences: atherosclerotic plaques that block blood flow through the vessels, blood carrying vital oxygen and nutrients. From the European Society of Cardiology, the vaccine’s newest clinical trial in humans is set to conclude at the end of the year.
A cross section of a mouse aortic blood vessel: in a mouse immunized with AT04A with little or no plaque. Image credit: The Netherlands Organisation of Applied Scientific Research
Before beginning the human trials, researchers studied the vaccine thoroughly in mice genetically altered to be prone to high levels of cholesterol. The mice were fed a fatty diet reminiscent of what many people who end up with high cholesterol levels choose, and this diet induced high cholesterol and atherosclerosis.
On a molecular level, the vaccine, made up of a chemical called AT04A, produces antibodies to inhibit an enzyme called PCSK9, a protein produced in the liver. PCSK9 expression prevents the body from eliminating “bad” cholesterol, low density lipoprotein (LDL) cholesterol (as compared to “good” cholesterol, high density lipoprotein (HDL)) by binding LDL cholesterol receptors and preventing other cells from clearing out LDL.
“As a consequence, levels of cholesterol were reduced in a consistent and long-lasting way, resulting in a reduction of fatty deposits in the arteries and atherosclerotic damage, as well as reduced arterial wall inflammation,” explained study author Dr. Gunther Staffler.
What causes a person to have high levels of LDL in the first place? Largely poor lifestyle choices. Genetics are also involved, like the inheritance of genes making a person more vulnerable to high LDL than others with different genes but similar lifestyles. Increasing rates of people with high cholesterol has led to more and more cases of atherosclerosis and other heart diseases. Drugs like statins are prescribed to lower LDL cholesterol, can cause negative side effects. Plus, statins are just a treatment for a largely preventable condition.
A Preventative Option: The Vaccine
During the trials in mice models, the AT04A vaccine was injected under the skin and over time produced very promising results:
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Total cholesterol reduced by 53 percent
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Atherosclerosis severity reduced by 64 percent
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Biological markers of blood vessel inflammation reduced by 21-28 percent
All of the changes in cholesterol and atherosclerosis were compared to mice induced to have high cholesterol and atherosclerosis but were not injected with AT04A. Additionally, the vaccine seemed to have a long-lasting effect, with reduction in dangerous markers increasing as the antibody concentration increased.
“We could develop a long-lasting therapy that, after the first vaccination, just needs an annual booster,” Staffler said about the human clinical trials. “This would result in an effective and more convenient treatment for patients, as well as higher patient compliance."
How is this therapy considered a “vaccine”?
"The way that AT04A is administered is comparable to a vaccine," Staffler explained. "However, the difference between a conventional vaccine and our approach is that a vaccine induces antibodies that are specific to bacterial or viral proteins that are foreign to the body - pathogens - whereas AT04A induces antibodies against a target protein that is produced by the body - endogenous proteins. This it is really an immunotherapeutic approach rather than a vaccine approach."
The human clinical trial to study the efficacy of AT04A in lowering LDL and reducing progression of atherosclerosis began in 2015 and is expected to be finished at the end of this year.
The present study is published in the European Heart Journal.
Source: European Society of Cardiology