Hopes rise for anti-cholesterol vaccine

200617 cholesterol 1
Artwork depicting low density lipoprotein – ‘bad’ cholesterol – in the bloodstream.

An initial clinical trial testing a vaccine that may protect people against high cholesterol levels is due to finish later this year.

In the meantime, the European Heart Journal features a paper by the vaccine’s inventors – a team led by Günther Staffler of Austrian pharmaceutical company AFFiRis – reporting the results of a trial using mice.

The vaccine, code-named AT04A, targets an enzyme called proprotein covertase subtilisin/kexin type 9 (PCSK9).

The enzyme binds to low-density lipoprotein receptors, reducing their ability to get rid of deposits of low-density lipoprotein cholesterol (LDL), the so-called “bad” cholesterol that if left untreated builds up in blood vessels, putting people at much greater risk of heart disease.

The primary current treatment uses statins, requiring people to take a daily pill.

Another promising approach is the use of monoclonal antibodies that target PCSK9. This has proved effective, but the results decline quite rapidly and the need for frequent renewal increases the cost.

Staffler and colleagues tested the AT04A on a cohort of genetically modified mice fed a diet heavy in fats to induce atherosclerosis – the build-up of fatty deposits in blood vessels.

The vaccinated mice carried 53% less cholesterol than controls, and had 64% less atherosclerotic damage.

At the end of the trial, antibody levels in the vaccinated mice remained high, leading Staffler to suggest the protective effect continues for a substantial period.

“If these findings translate successfully into humans, this could mean that, as the induced antibodies persist for months after a vaccination, we could develop a long-lasting therapy that, after the first vaccination, just needs an annual booster,” he says.

Development of the vaccine has been under way for quite some time. The clinical study to test its safety in humans, which kicked off in 2015 at the Medical University of Vienna, due to conclude in a few months.

An editorial accompanying the journal report, written by Ulrich Laufs of Germany’s Leipzig University and Brian Ference of Bristol University in England, cautiously welcomes the advent of an anti-cholesterol vaccine.

However, the pair urge further research, noting that decreasing levels of PCSK9 have been linked to increased risk for diabetes.

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