Cholesterol-lowering vaccine shows promise in mice

A new clinical trial from the Netherlands Organisation of Applied Scientific Research is testing the efficacy of a vaccine that will immunize people against high levels of cholesterol and atherosclerosis. So far, it’s yielded positive results in mice models, providing hope for a version that can treat these deadly conditions in humans.

The trial, published June 20 in the European Heart Journal, is the first to show that it’s possible to immunize genetically modified mice with a molecule that causes the body to produce antibodies against PCSK9 (proprotein covertase subtilisin/kexin type 9). The enzyme plays a role in extracting bad cholesterol from the blood.

Findings showed that the AT04A vaccine reduced the total amount of cholesterol by 53 percent, atherosclerotic damage to blood vessels by 64 percent and biological markers of blood vessel inflammation by 21-28 percent, compared to mice that hadn’t received the vaccine.

The vaccine works by inducing antibodies that specifically target PCSK9, which results in a reduction of fatty deposits in the arteries, atherosclerotic damage and arterial wall inflammation.

"The reduction in total cholesterol levels was significantly correlated with induced antibody concentration, proving that induced antibodies caused the reduction in cholesterol and also are ultimately responsible for the reduction of atherosclerosis development,” said study author Günther Staffler, MD, in a statement. “As antibody concentrations remained high at the end of the study, it can be assumed they would continue to reduce cholesterol levels for some time afterwards, resulting in a long-lasting effect, as has been shown in previous studies.”

Looking ahead, the researchers wants to explore if the findings from this mouse trial could translate successfully into humans. If they do, a long-lasting therapy could be developed to prevent cholesterol and atherosclerosis.

"The way that AT04A is administered is comparable to a vaccine," Staffler said. "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."