Tuesday June 20 2017
Human trials for the new jab are underway
“Cholesterol-lowering jab to help prevent heart disease,” reports BBC Online.
The headline refers to a recent mouse study that aimed to see whether a new vaccine could reduce cholesterol and lower the risk of heart disease.
Mice bred to develop heart and vascular disease were given the AT04A vaccine or a control vaccine, and were then fed a high-fat diet for 18 weeks.
The research found that, compared with the control, the vaccine reduced total and LDL cholesterol levels in the mice, as well as reducing signs of fatty build-up in the arteries.
The vaccine has now moved on to the first stage of human trials to see if it’s safe to use in humans.
If this shows promise, there would then be more trial stages to see if it’s safe and effective at lowering cholesterol, and how it compares with statins and other newer drugs already licensed to treat LDL cholesterol.
These trials can take years and, although the vaccine showed promising results in mice, there’s no guarantee this will ever become a licensed vaccine for use in humans.
Where did the story come from?
The study was carried out by researchers from several institutions, including Leiden University Medical Center and the Netherlands Organization of Applied Scientific Research (TNO) in the Netherlands.
Four of the researchers are also employees of AFFiRiS, the biotech company responsible for inventing and developing the vaccine currently under trial. AFFiRiS also partially funded this study.
Although some media coverage implied that this vaccine was coming on to the market very soon, most of the reporting was accurate and made it clear that this research is still in its early stages.
What kind of research was this?
This animal study evaluated the potential of the AT04A vaccine to reduce cholesterol and signs of heart and vascular disease in genetically engineered mice.
High blood cholesterol levels – particularly high levels of low density lipoproteins (LDL), also known as “bad” cholesterol – are linked to cardiovascular disease, including stroke and heart attacks.
The new AT04A vaccine works by blocking an enzyme called proprotein convertase subtilisin/kexin type 9 (PCSK9), which stops LDL cholesterol being cleared from the body.
Animal studies are useful for giving an indication of whether new treatments have potential for humans. But even though mice and humans have similarities, we aren’t identical.
Animal research is the very first step in trialling a drug or vaccine to see whether it’s safe and effective enough to move on to human trials. After that, there are many more stages of development before it can be licensed for use in humans.
Only a very small proportion of animal research makes it through to this stage.
What did the research involve?
The researchers used 7-9-week-old mice bred to develop heart and vascular disease or atherosclerosis (a build-up of fatty material inside the arteries).
These mice were then either immunised with AT04A or given a control vaccine. The vaccine was given five times at twice-weekly intervals.
For the first four weeks after the first vaccine shot was given, the mice were fed a normal diet. After this they were put on a high-fat, high-cholesterol diet for 18 weeks.
Blood samples were taken to analyse cholesterol levels at the start of the trial prior to vaccination and then every four weeks for the remainder of the trial.
At the end of the 18-week trial, researchers also analysed the level of atherosclerosis in the aorta, the large artery coming out of the heart.
The data for mice immunised with AT04A was compared with mice given the control vaccine.
What were the basic results?
The research showed that the AT04A vaccine was able to induce a successful and long-lasting immune response.
Mice given the vaccine started to produce antibodies against PCSK9. This wasn’t seen in mice immunised with the control.
Mice vaccinated with AT04A showed a significant reduction in total blood cholesterol levels, with a 53% reduction at week 18 compared with mice in the control group (AT04A: 7.8mM versus control: 12.1mM).
The AT04A vaccination had no effect on high density lipoprotein (HDL), or “good” cholesterol, levels. But it did reduce LDL levels compared with the control group.
AT04A was found to reduce the overall area of atherosclerosis in the aorta by 64% compared with the control group. It also reduced biological markers of blood vessel inflammation by 21-28%.
How did the researchers interpret the results?
The researchers concluded that, “The present study shows that active immunisation against PCSK9 with the [AT04A vaccine] elicits antibodies that effectively bind and remove PCSK9 from the circulation and reduce circulating [cholesterol] and biomarkers of inflammation, which is accompanied by reduction of vascular inflammation and atherosclerotic lesions in the aortas of a mouse model of atherosclerosis.”
This mouse study evaluated the potential of the AT04A vaccine to lower cholesterol levels and potentially reduce or prevent heart disease.
The results were promising, showing that mice given the vaccine produced antibodies against the enzyme that stops LDL cholesterol being cleared from the body. This resulted in reduced total and LDL blood cholesterol levels, as well as reduced atherosclerosis.
No major safety concerns or side effects were reported.
Following this research, AT04A has now moved on to a phase I clinical trial. A small number of people will be given the vaccine to see if it’s safe for use in humans.
If it’s shown to be safe, the next step would be to carry out a trial in a slightly larger number of people.
If this shows promise, it could then move to larger randomised controlled trials comparing the vaccine with other established cholesterol treatments, such as statins.
If further trials are successful, the AT04A vaccine could be a safe, cost effective way of lowering LDL cholesterol and preventing and treating heart disease.
But it’s far too early to know at this stage. There are many more trials to go, and it’ll probably be years before it’s known if this could be a new vaccine licensed for use in humans.
For now, the best way to control your cholesterol level is to eat a balanced diet, stay physically active, and not smoke.
See more tips on preventing high cholesterol.