How vaccines could be about to revolutionise acne treatments

It’s a cruel twist. Just as we become more concerned about our appearance, our faces start to erupt in great red spots. Pimples cause anguish for many teenagers and can persist into adulthood too. But now two companies are developing vaccines that they hope will revolutionise the treatment of acne. Is an end to the misery at hand?

The main idea behind this new approach is that acne is caused by the immune system overreacting to proteins released by skin bacteria. Triggering the body to produce antibodies against these proteins should block this process and prevent – or at least reduce – acne. Pharma giant Sanofi is preparing for trials in the US and Canada of an mRNA vaccine targeting at least one bacterial protein, while US start-up Armora Biosciences is focusing on a different protein.

Better treatments for acne are certainly needed. “Acne causes a significant emotional burden,” says Tomasz Zastawny at Armora. “It can lead to the development of depression, social isolation and other psychological outcomes as well.”

It has been known for decades that acne is linked to the presence of a bacterium called Cutibacterium acnes, which thrives deep in hair follicles where there is little oxygen. But C. acnes is the most common skin bacterium, present on just about everybody – including those that don’t have acne – so there’s a lot more to it.

One factor is the surge in hormones during puberty, which increases the production of fatty substances in the skin, affecting bacterial growth. But not everyone gets pimply during adolescence, so there seem to be genetic factors involved as well.

“Acne is very complicated. It’s not an infection,” says Richard Gallo at the University of California, San Diego. “It’s an immune problem.”

In other words, while the presence of C. acne doesn’t usually cause problems, sometimes it may trigger a strong immune response inside a follicle. During this response, some cells in the skin actually turn into fat cells and start releasing alarm signals and antimicrobial substances – a process known as reactive adipogenesis. “This is a normal way to fight an infection, but in this case, it’s an inappropriate response,” says Gallo.

What triggers that response? C. acnes can secrete a toxin known as Christie-Atkins-Munch-Petersen factor, or CAMP. The bacteria may ramp up production of CAMP in certain circumstances.

So, Gallo’s team tried vaccinating mice against CAMP, to make the animals produce antibodies that neutralise the toxin. A number of studies by his team suggest this could help prevent or treat acne.

Sanofi has now developed an mRNA vaccine that targets CAMP, possibly along with some other C. acnes proteins – the company hasn’t revealed exactly what’s in the vaccine and, after much back and forth, declined to talk to me about it.

While there have been reports that the Sanofi trial is already underway, it is labelled as “not yet recruiting” as per the latest update on 18 September. This means it may be some time before we know if it works. That said, while these initial trials are primarily intended to establish safety, it should be clear to volunteers within weeks if it is making a difference to their acne – this isn’t like a normal vaccine trial where researchers have to wait months or years for people to be exposed to pathogens.

“We were very, very optimistic that this could be revolutionary for acne therapy,” says Gallo. “We’ll just have to see if it pans out in the human population.”

Meanwhile, Armora is targeting a different protein, called hyaluronidase, based on work by George Liu at the University of California, San Diego. Hyaluronidase is an enzyme that breaks down hyaluronic acid, a large sugar secreted into the spaces between cells. These terms might be familiar because hyaluronic acid is often used as a filler for cosmetic purposes, while hyaluronidase is injected to break down filler that is no longer wanted or if things go wrong.

Some bacteria such as strep B (Streptococcus agalactiae) produce hyaluronidase for similar purposes, to help them invade tissues. There are two main types of hyaluronidase, it turns out. Some break down hyaluronic acid into simple sugars. Others break it up into large chunks that act as an alarm signal to the immune system.

When it became clear that there were two types, Liu’s team searched genetic databases to see which type is found in which bacteria. They found the “simple sugars” type was the most common. The “large chunks” type was limited to a few free-living bacteria, which makes sense because they don’t need to worry about immune systems.

“The exception was acne,” says Liu. C. acnes jumped out to the researchers because it produces both types of hyaluronidase. More precisely, some strains of C. acne produce the simple-sugars type, while other produce the large-chunks one – none produce both, he says.

That made Liu wonder if this was connected to acne. Sure enough, the team showed in mouse studies that large-chunks strains of C. acnes cause acne-related inflammation, while the simple-sugars one slightly reduces inflammation. The team then went to show that a vaccine that stimulates the production of antibodies targeting only the large-chunks form of hyaluronidase could reduce acne in mice, as could inhibiting the enzyme with a small protein.

What isn’t clear is why some strains of C. acnes have evolved to trigger an immune response. One possibility is that it is a way to kill off some of their competitors, says Liu.

He thinks that in people, a vaccine against the large-chunks form of hyaluronidase would be most effective against the “more severe, red, angry type of acne lesion”.

“The ones that are hard to treat right now, those are the ones that we would target with a vaccine,” he says.

His findings might also help explain why antibiotics, which are commonly prescribed for acne, don’t work that well: they kill off the helpful C. acnes strains as well as the harmful ones. The other issue with antibiotics, of course, is that resistance can develop.

Another acne treatment called isotretinoin (Roaccutane) is more effective than antibiotics but has a long list of nasty side effects including causing birth defects, impotence and dry, itchy skin. How it works isn’t clear, though there is some evidence it alters the skin microbiome.

Acne vaccines promise to solve all these issues. They shouldn’t have any lasting side effects, nor should there be any issue with resistance, because the vaccines are targeting secreted proteins rather than directly targeting bacteria.

The fact that two competing approaches are being developed is great news for those with acne. If one vaccine doesn’t work, perhaps the other will. And it could be that both will work, or that targeting both CAMP and hyaluronidase simultaneously will prove even more effective than either alone. Maybe, just maybe, adolescence is about to get a little easier.