Heart and lungs

Will a cholesterol-busting vaccine work for humans?

"Could a vaccine replace the need for daily statins?" asks the Mail Online. An experimental vaccine has been found to lower low-density lipoprotein (LDL) cholesterol in a small number of mice and macaque monkeys, but has not yet been tested in humans.

LDL cholesterol – aka "bad" cholesterol – can clog up the arteries, leading to conditions such as heart attack and stroke. Currently, a group of drugs known as statins are used by several million people in the UK to lower LDL cholesterol.

The new research tested several types of vaccine, designed to target a protein called PCSK9. This protein helps regulate how much LDL cholesterol is in the blood. It does this by blocking receptors in the liver that absorb it and break it down.

Previous studies showed people with naturally occurring mutations that stop PCSK9 working had low levels of LDL cholesterol and remain healthy.

The vaccine is designed to provoke an immune response against PCSK9. The researchers found several of the vaccines worked in mice and monkeys, reducing their LDL cholesterol level. A combination of vaccine and statins tested in monkeys resulted in lower levels of LDL cholesterol than the vaccine alone.

If further studies show this vaccine is safe and effective in humans, it could be a useful additional treatment. Some people find statins hard to tolerate, complaining of side effects such as muscle and joint pain, and weakness. A vaccine could prove to be an alternative form or treatment.  

Where did the story come from?

The study was carried out by researchers from the University of New Mexico and the National Institutes of Health in the US, and was partly funded by these institutions.

It was published in the peer-reviewed medical journal Vaccine on an open-access basis, so it can be read online for free.

The researchers have applied for a patent for the vaccines, which represents an obvious – though understandable and reasonable – conflict of interest.

The Mail Online and The Daily Telegraph predicted the vaccine would eventually replace statins, although nothing in this study suggests this. The Telegraph reported the vaccine "can lower cholesterol better than statins".

However, this is patently not the case – the study actually showed the injection reduced cholesterol by only 10-15% in monkeys, less than the 20-50% reduction that usually occurs in humans taking statins, depending on the type and dose of statin. 

What kind of research was this?

This animal study used mice and macaque monkeys to test experimental vaccines developed in the laboratory.

Animal studies are done at an early stage in the development of new treatments. They don't tell us whether the treatment is safe or effective in people. 

What did the research involve?

Researchers developed two types of vaccine and tested them firstly on mice, along with a dummy vaccine, then on nine macaque monkeys. They later did a second experiment with the monkeys, which combined a booster dose of the vaccine with treatment with statin drugs, to see whether the two worked well in combination to lower cholesterol.

The vaccines were designed to mimic a virus, with features of the PCSK9 protein on the surface. The researchers hoped the animals' immune systems would produce antibodies to disable the PCSK9 protein.

They predicted this would result in more LDL cholesterol being taken out of the blood, so cholesterol levels would fall. They also used a dummy vaccine without PCSK9 features as a control.

In the first experiment, the researchers used mice split into groups of five, and compared the effects of several variations on the vaccine, plus the dummy vaccine for comparison. They measured the mice's antibodies and their cholesterol and other lipid levels before and after the vaccine.

They researchers repeated the experiment by using the most successful vaccine on 20 mice. They then used the vaccines and dummy vaccine on nine monkeys, split into three groups, again measuring antibody levels and cholesterol.

Finally, they revaccinated the monkeys and gave them statins for two weeks to see the effect of combined treatment on their cholesterol levels. They looked at which vaccines had most effect on lipid levels, and whether they had a significant effect on LDL cholesterol levels.  

What were the basic results?

The mice and monkeys given the anti-PCSK9 vaccines produced antibodies to PCSK9, although, unsurprisingly, not in those animals given the dummy vaccine.

In mice, cholesterol levels dropped significantly for those treated with four of the seven anti-PCSK9 vaccines. Mice who'd had the most successful of the two vaccines showed a 55% drop in total cholesterol in the first experiment and a 28% drop in the second experiment, compared with the group given the dummy vaccine.

The monkeys had a smaller response. Monkeys given one of two anti-PCSK9 vaccines showed drops in total cholesterol of 10-15%, compared with those given the dummy vaccine.

When the vaccine was combined with a two-week course of statins, LDL cholesterol dropped by 30-35% more than in monkeys who'd been given the dummy vaccine plus statins, although the difference for total cholesterol was only about 15-20%. 

How did the researchers interpret the results?

The researchers say their study "provides proof-of-principle evidence that a vaccine targeting PCSK9 can effectively lower lipid levels and work synergistically with statins". They say their study has helped them identify "at least one" candidate vaccine to study further.

They say they should now be able to do a study in humans to check for the safety of the vaccine. They concluded: "If successful, this approach could obviously have a major impact on human health worldwide." 


The first thing to keep in mind is this is an early-stage study in the development of a vaccine to lower cholesterol. The study found some of the experimental vaccines the researchers developed had an effect on the cholesterol levels of mice and monkeys to varying degrees.

They now need to do further work to show the vaccine is effective and can be used safely in humans. Many drugs have very different effects in humans than they do in other animals.

The use of statins to lower cholesterol and reduce the chances of a heart attack or stroke is well established and effective for many people. Although there is ongoing controversy about the side effects of statins, they have been used for decades, and their benefits and risks are reasonably well understood.

The type of vaccine being explored in this study works to "prime" the immune system to attack a naturally occurring protein in the body. While some people seem to remain healthy despite having been born without a functioning version of this protein, and indeed have a lower risk of heart disease, we don't yet know what the long-term effects of a vaccine that works in this way would have.

The next crucial stage of research must be to establish the safety of this proposed new vaccine in humans. Until we know it is safe in people, there's not much point in speculating about how it could be used in the future.

If you are unable or unwilling to take statins, there are alternatives that can reduce your cholesterol, including alternative medicines such as fibrates, as well as lifestyle measures. 

NHS Attribution