Vaccination against high cholesterol

Researchers at the University of New Mexico and the US National Institutes of Health have developed a vaccine to lower cholesterol levels in the blood. A vaccine that selectively affects the PCSK9 molecule – a protein involved in cholesterol metabolism – is a cost-effective alternative to modern expensive drugs.

Genetic mutations that increase the activity of PCSK9 are associated with elevated levels of low-density lipoproteins or "bad" cholesterol, which, in turn, are associated with an increased risk of plaque deposition on the inner surface of the arteries, leading to the development of coronary heart disease and stroke.

Despite the fact that lifestyle adjustments and medications (such as statins) can help in lowering cholesterol levels in the blood, more than 60% of patients at risk of cardiovascular pathology develop, despite the use of cholesterol-lowering therapy.

Statins have side effects, including increased levels of liver enzymes, muscle pain, impaired cognitive function, increased risk of diabetes and undesirable interactions with other drugs. As an alternative to statins, pharmaceutical companies have developed drugs based on monoclonal antibodies that affect the PCSK9 protein, such as alirocumab (Alirocumab) and evolocumab (Evolocumab). These drugs have recently been approved by the US Food and Drug Administration as a means to reduce cholesterol levels in the blood.

Drugs based on monoclonal antibodies can significantly reduce the level of low–density lipoproteins in the blood (by 60%), but they are extremely expensive - an annual course of admission costs more than $ 100,000. This, as well as the need for regular therapy, severely limits the use of drugs of this class by patients who do not respond to statins and take other drugs to reduce cholesterol levels in the blood.

The vaccine proposed by the authors as an alternative contains virus-like particles that are immunogenic carriers of the PCSK9 antigenic peptide. Virus-like particles are viral particles, part of whose DNA has been removed in such a way as to preserve their external structure to represent the antigen, while simultaneously depriving them of the ability to replicate. They can trigger an immune response without causing infection. Vaccines based on virus-like particles are effective and safe, while their development and production do not require large costs.

As part of the study, mice and macaques were injected with vaccines containing virus-like particles created on the basis of a bacteriophage presenting PCSK9 peptide fragments. As a result, the animals formed high titers of antibodies represented by immunoglobulin G, binding the PCSK9 protein circulating in the blood. Vaccination provided a significant reduction in the blood content of total cholesterol, free cholesterol, phospholipids and triglycerides.

The developers believe that their proposed vaccine will eventually give rise to a widely used method of controlling hypercholesterolemia and preventing diseases of the cardiovascular system.

Article by Erin Crossey et al. A cholesterol-lowering VLP vaccine that targets PCSK9 is published in the journal Vaccine.

Evgeniya Ryabtseva
Portal "Eternal youth" http://vechnayamolodost.ru