Acne Vaccines Could Offer Robust Defense

Acne Vaccines Could Offer Robust Defense

By Benjamin Plackett

This article is part of Nature Outlook: Skin, an editorially independent supplement produced with financial support from LEO Pharma. About this content.

Acne has long been dismissed as an unfortunate cosmetic issue — a rite of passage that is ultimately of little importance. But that attitude is changing. Many scientists now accept that acne is an attention-worthy condition.

Roughly 80% of adolescents worldwide experience acne, which can persist into later adulthood. Because the onset of acne can coincide with the stage of development when self-image is forming, outbreaks “can lead to social withdrawal, low self-esteem and even depression”, says dermatologist Anjali Mahto, spokesperson for the London-based British Skin Foundation.

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Topical treatments for acne offer only partial and temporary reductions in symptoms. Even the antibiotic isotretinoin, which carries significant side effects, is just a short-term solution — acne often rebounds a few months after treatment ends. There is, therefore, considerable need for treatments that can truly banish acne, rather than mask it.

Leading that charge are two vaccine candidates that aim to engage the immune system in tackling the underlying cause of acne. Acne is influenced by hormones and genetics, but it is driven by inflammation and lesions caused by bacteria that grow in clogged pores. The vaccines — one that would treat the condition and one that would act as a preventive measure — both attempt to provoke the immune system into targeting these acne-causing bacteria. “It has taken time for the field to treat acne as a disease of immune regulation, rather than just a surface issue,” says Mahto. “What matters most is this shift in mindset.”

Messenger RNA money maker

In the United States, people with acne typically spend as much as US$200 each year on over-the-counter products designed to treat blemishes. Isotretinoin can cost as much as $3,000 for a four-to-six-month course. The global market size for acne drugs was estimated at $9.22 billion in 2023, and is expected to grow by about 5% annually for the rest of this decade. Pharmaceutical firm Sanofi in Paris suggests that the acne vaccine it is developing could yield more than $2 billion per year in revenue.

The company is recruiting up to 400 people with moderate to severe acne in the United States to take part in a phase I clinical trial for its therapeutic vaccine. Participants will be given two injections initially and a booster shot one year later. Sanofi intends to recruit a further 200 people with mild acne for a second clinical trial in Singapore.

These trials follow Sanofi’s experiments with the acne-prevention agent in mice. Researchers tested two versions of the vaccine in the animals: one containing protein fragments from the bacteria associated with acne, and the other made up of pieces of messenger RNA that encode these proteins. After injecting the mice, the team checked to see whether the animals had produced antibodies. Acne-causing bacteria were then exposed to those antibodies in the laboratory to verify that the antibodies could limit the growth of the bacteria. The mRNA vaccine was shown to be the more effective of the two, and is the version that is now being tested in humans. “If we can reduce antibiotic use, we not only create value for the people who take the vaccine, but also for society as well, by reducing microbial resistance,” says Jean-François Toussaint, who heads vaccine research and development at Sanofi.

A prevention rival

Paediatrician George Liu at the University of California, San Diego, and his colleagues are also working on an acne vaccine — but they have taken a different approach (I. A. Hajam et al. Nature Commun. 14, 8061; 2023).

Instead of using mRNA, they are targeting an enzyme called hyaluronidase, which is secreted by acne-causing bacteria. Hyaluronidase breaks down hyaluronic acid, a protective substance produced by the skin. This triggers the inflammatory response that manifests as acne. Liu is hoping to disrupt the biochemical pathway that culminates in this inflammation.

His team injected mice with fragments of hyaluronidase and smeared the animals’ skin with an oily substance to mimic the conditions of human skin. The scientists then modelled acne in mice by infecting the animals’ humanized skin with the bacteria; mice in a control group were similarly infected, but did not receive the vaccine. The result clearly showed that the vaccine prevented the onset of acne in mice. It does this, says Liu, by inducing antibodies that bind to the enzyme and neutralize it. Unlike Sanofi’s vaccine, which is intended to treat people with acne, Lui’s would be used mainly for prevention.

One of the challenges that both efforts will face is the rise of vaccine hesitancy. In a 2024 telephone poll by global analytics firm Gallup, of 1,010 US adults, just 40% said it was ‘extremely important’ for parents to get their children vaccinated for serious diseases such as measles (see go.nature.com/4ietfak). If this is how people feel about lifesaving vaccines, an acne shot might be a hard sell.

But Mahto sees an opening. “It depends on how the vaccine is positioned and communicated,” she says. “These vaccines are not being proposed as part of a national immunization programme — they would be optional.” The lack of an effective alternative could motivate many people to have it, she says. “If a vaccine were safe, effective and offered longer-term remission without the need for ongoing medication, many would be open to it.”

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