The new vaccine was found to dramatically reduce cholesterol in mice and monkeys, suggesting it could do the same for humans.
In the journal Vaccine, study coauthor Dr. Bryce Chackerian - of the Department of Molecular Genetics and Microbiology at the University of New Mexico - and colleagues reveal how the new vaccine significantly reduced low-density lipoprotein (LDL) cholesterol in both mice and rhesus macaque monkeys.
LDL cholesterol is commonly referred to as "bad" cholesterol; high levels of LDL cholesterol can cause a build-up of plaque in the arteries, increasing the risk of heart attack, stroke and heart disease - the leading cause of death in the US.
According to the Centers for Disease Control and Prevention (CDC), people with high LDL cholesterol are twice as likely to develop heart disease than those with normal levels.
While lifestyle changes, such as adopting a healthy diet and increasing physical activity, are key for maintaining normal cholesterol levels, many people take statins to lower LDL cholesterol. Statins work by blocking an enzyme needed by the liver to produce cholesterol.
Though statins can be effective, Dr. Chackerian and colleagues note that they do not work for everyone and may cause severe side effects, including muscle pain, liver damage, digestive problems and increased diabetes risk.
But the team says their vaccine - which works by inhibiting a cholesterol-regulating protein in the blood called PCSK9 (proprotein convertase subtilisin/kexin type 9) - may provide a more effective alternative to statins.
Vaccine 'could have a major impact on health worldwide'
For their study, the researchers created a bacteriophage virus-like particle (VLP) vaccine that produces strong antibody responses against PCSK9.
PCSK9 works by binding to the LDL cholesterol receptor in the blood. In the liver, the LDL receptor effectively removes LDL cholesterol from the blood, but when PCSK9 binds to it, it no longer has this ability. By blocking PCSK9 - which the new vaccine does - the LDL receptor can do its job.
Fast facts about cholesterol
- Less than half of adults in the US with high LDL cholesterol are receiving treatment for it
- However, the percentage of Americans receiving treatment for high LDL cholesterol has increased, from only 28.4% in 1999-2002 to 48.1% in 2005-08
- All adults should have their cholesterol levels checked every 5 years.
On testing a single dose of the vaccine in 4-6-week-old mice, the team found it significantly reduced LDL cholesterol levels. When combined with statins, the team found the vaccine produced an even greater reduction in LDL cholesterol among 9-17-year-old rhesus macaques. The findings suggest the vaccine may also lower cholesterol in humans, according to the researchers.
"One of the most exciting things about this new vaccine is it seems to be much more effective than statins alone," notes Dr. Chackerian.
The new vaccine is the not the first cholesterol-lowering treatment to be developed that targets PCSK9. In August, the US Food and Drug Administration (FDA) approved a drug called evolocumab (brand name Repatha) that uses monoclonal antibodies to block PCSK9 and lower LDL cholesterol.
The FDA approved the drug to be used alongside a healthy diet and maximally-tolerated statin therapy for adults with a genetic predisposition for high cholesterol, as well as heart attack and heart disease patients who require further lowering of LDL cholesterol.
However, Dr. Chackerian and colleagues believe their vaccine may not only be more effective than such treatments, but it may also be a much cheaper alternative, noting that monoclonal antibody-based therapies can cost a patient more than $10,000 annually.
"While the developed world may be able to sustain these costs, expense is likely to be a major impediment to the use of such drugs in the developing world," say the authors. "In contrast, vaccination for a wide variety of mostly infectious communicable diseases has been proven to be compatible with the health care infrastructure in the developed and developing world."
Commenting on their overall findings, the researchers say:
"The data reported here, in both mice and macaques, provides proof-of-principle evidence that a vaccine targeting PCSK9 can effectively lower lipid levels and work synergistically with statins.
Thus, the use of VLP-based vaccines targeting PCSK9 peptide could serve as a cost-effective alternative to other therapies and could lead to a widely applicable vaccine-based approach for controlling hypercholesteremia [high cholesterol] and cardiovascular disease. If successful, this approach could obviously have a major impact on human health worldwide."
The researchers plan to conduct further testing of the vaccine in macaques, and they hope to move forward with vaccine development by teaming up with commercial partners.