Scientists Develop LDL Cholesterol-Lowering Vaccine

A new virus-like particle-based vaccine leads to dramatic reductions in ‘bad’ LDL cholesterol in mice and macaques, says a team of scientists led by the University of New Mexico and NIH’s Lung and Blood Institute.

This image shows that high levels of active PCSK9 gene (green color) prevent LDL cholesterol (red color) from binding to the surface of liver cells. Image credit: Rockefeller University.

LDL (low-density lipoprotein) cholesterol, also known as ‘bad’ cholesterol, makes up the majority of the body’s cholesterol.

A high LDL cholesterol level is considered a risk factor for coronary artery disease because, under certain conditions, it can cause hardening of the arteries.

According to the CDC, 73.5 million adults (31.7%) in the United States have high LDL cholesterol and fewer than 1 out of every 3 adults (29.5%) with high LDL cholesterol has the condition under control.

Diet and exercise are key to keeping cholesterol down, but millions of people worldwide take statins, a family of medications that lower cholesterol. Even more important, statins lower the chances of having a heart attack or stroke. They include atorvastatin, fluvastatin, lovastatin, pitavastatin, pravastatin, rosuvastatin, and simvastatin.

However, they have some potentially serious side effects, such as muscle pain, an increased risk of diabetes and cognitive loss.

The newly developed vaccine could provide an alternative to statins, by targeting a protein that controls cholesterol levels in the blood.

“One of the most exiting things about this new vaccine is it seems to be much more effective than statins alone,” said Dr Bryce Chackerian, a scientist at the University of New Mexico and lead author of a study in the journal Vaccine.

The new vaccine targets a protein called proprotein convertase subtilisin/kexin type 9 (PCSK9), which regulates the cholesterol in the blood.

“PCSK9 is a secretory protein that controls cholesterol homeostasis by enhancing endosomal and lysosomal degradation of the low-density lipoprotein receptor,” the scientists explained.

People who have a mutation in the protein often suffer from increased risk of heart disease, and people who do not produce the protein have a decreased risk.

By targeting PCSK9, the vaccine can stop it from functioning, lowering the amount of cholesterol in the blood.

Dr Chackerian and his colleagues tested the vaccine in mice, which showed a reduced level of LDL cholesterol. They then tested it in a small group of macaques, along with statins, resulting in a dramatic decrease in cholesterol.

“Mice and macaques vaccinated with bacteriophage VLPs displaying PCSK9-derived peptides developed high titer IgG antibodies that bound to circulating PCSK9,” Dr Chackerian and co-authors said.

“Vaccination was associated with significant reductions in total cholesterol, free cholesterol, phospholipids, and triglycerides.”

“A vaccine targeting PCSK9 may, therefore, be an attractive alternative to monoclonal antibody-based therapies.”

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Erin Crossey et al. 2015. A cholesterol-lowering VLP vaccine that targets PCSK9. Vaccine, vol. 33, no. 43, pp. 5747-5755; doi: 10.1016/j.vaccine.2015.09.044