Swedish teams propose vaccines against heart disease
course of vaccinations in childhood might help protect people from
heart disease later in life.
The concept was put forward late last year at a session of the European Vascular Genomics Network in Cambridge, UK, where the first animal studies from this vaccination approach were presented.
The team from the Karolinska Institute in Sweden, headed by Goran Hansson, are trying to develop a vaccine that can prevent the formation of the fatty deposits in the blood vessels - atherosclerotic plaques - that are at the root of many heart attacks.
Most heart attacks are caused by blood clots in the heart's arteries that cut off the blood supply to the organ's muscles. The trigger is often the rupture of fatty plaques lining the arteries, which releases a 'gruel' of phospholipids and proteins that attract blood platelets and trigger the formation of clots.
Many groups worldwide are working on ways to prevent the formation of these plaques. The process involves a complex interaction between the immune system and low-density lipoprotein (LDL), which carries cholesterol in the blood.
About 10 years ago, Jan Nilsson at Lund University in Sweden tried to provoke this immune response by giving oxidised LDL to mice. Oxidised LDL is the main form of the protein found in plaques, so Nilsson expected to see more atherosclerosis. But he was wrong. "To our surprise the mice were protected," he said.
This started him thinking that patients could be vaccinated against atherosclerosis, an idea that his group and Hansson's group have been working on independently. Both teams are using fragments of the oxidised form of LDL to prime the immune system to attack plaques when they first begin to form.
To test the idea, they have been injecting groups of mice with LDL fragments or a control. The mice given the LDL vaccination show as much as a 70 per cent reduction in the number of plaques, and existing plaques appeared to stop growing, Nilsson and Hansson reported at the Cambridge meeting. There were no signs of any ill effects.
Nilsson has gone further by exploring whether injecting antibodies to LDL fragments, rather than waiting for the body to produce them after vaccination, also works. Initial experiments in mice suggest they are almost as effective in the short term as the vaccination.
To develop the idea further, Nilsson has teamed up with the Swedish company Bioinvent. Nilsson and Hansson hope initial trials on human volunteers could begin within two years. But nobody yet understands the mechanisms involved, or if the approach will work in humans.
"It is an extremely attractive idea," said UK cardiologist Andrew Newby of Bristol Royal Infirmary in the UK, who chaired the meeting where the vaccine research was presented. "In principle it would be a relatively short-term treatment, but give lifetime protection."
The number of atherosclerotic cases in 2000 totalled nearly 174 million in the major pharmaceutical markets. This figure will increase owing to the ageing population. However, the true frequency of atherosclerosis is difficult to accurately determine because it is a predominantly asymptomatic condition.
In the US, approximately 1.5 million myocardial infarctions occur annually, indicating that unstable atherosclerotic plaques affect about 50 per cent of the population.
The current gold standard for the treatment of atherosclerosis are the statins, the second largest selling drug class in the world. However, a large part of individuals who are on statin treatment may still have catastrophic events (heart attacks or stroke) as the level of oxLDL (oxidised aggregate of lipids, cholesterol and protein) is not affected. BioInvent believes that oxLDL is the key determent of unstable plaques and sp aims to develop a treatment that specifically removes the oxLDL from circulation in serum.
