Goodbye to spots? A revolution in acne vaccines is on the way

It is one of the cruellest ironies of human biology: just at the age when we start to worry desperately about our appearance and our first social interactions, our facial skin decides to rebel, turning into a minefield of inflamed spots. Acne is not merely a passing cosmetic nuisance. For millions of teenagers, and an ever-increasing number of adults, it represents an emotional ordeal capable of opening the floodgates to anxiety, social isolation and deep depression. For decades, medicine has responded with ointments, prolonged courses of antibiotics or aggressive systemic drugs. Today, however, the real breakthrough could come from an unexpected direction: therapeutic vaccines. Two cutting-edge strands of research, to which New Scientist has dedicated an extensive feature to, are in fact redefining the biological basis of the condition, focusing on mRNA formulations and selective antibodies capable of quelling inflammation without wreaking havoc on our skin’s ecosystem.

For generations, we have been told that acne is caused by pores blocked by sebum and an invading bacterium: Cutibacterium acnes. Yet this microorganism is present on the skin of almost everyone, including those with a complexion as smooth as porcelain. If the bacterium is everywhere, why do only some people suffer from painful breakouts? “What clearly emerges from these studies is a genuine paradigm shift,” emphasises Caterina Longo, full professor of Dermatology at the University of Modena and Reggio Emilia. “It is no longer just about the presence of C. acnes, but about the balance between different bacterial strains and the host’s response,” she adds. As Richard Gallo of the University of California, San Diego explains, “acne is not a trivial infection, but an altered immune response”. During puberty, the surge in hormones stimulates the glands to produce an abundance of sebum in the hair follicles. In some individuals, the immune system reacts abnormally to the proteins secreted by the bacterium through reactive adipogenesis: some skin cells temporarily transform into fat cells, releasing molecular alarm signals and triggering a cascade of inflammatory mediators. A normal defence against aggressive infections which, in this case, results in a short-circuit that is damaging to the tissues.

This reaction is often triggered by a specific toxin released by C. acnes, known as the CAMP factor. Researchers in San Diego and other independent studies have shown in mice that, by stimulating the body to produce antibodies specifically targeting the CAMP factor, inflammation is significantly reduced. “The use of this factor as a vaccine target is backed by solid scientific evidence,” explains Longo. On this basis, the pharmaceutical giant Sanofi has developed an mRNA vaccine candidate. “Sanofi’s Phase 1–2 trial is very ambitious: it plans to enrol around 800 adults aged between 18 and 45 with moderate-to-severe acne,” explains Longo. “We are not talking about teenagers at the moment, but about an adult population, where, moreover, the condition is common in both men and women and often manifests with specific patterns of distribution, such as in the jawline area,” she adds. Nor is this a preventative vaccine in the traditional sense. “We shouldn’t think of it as an injection that prevents acne from appearing,” clarifies the dermatologist. “It will be a therapeutic vaccine: an option for those who already have moderate or severe inflammatory acne, designed to reduce lesions and prevent permanent scarring,” she adds.

Alongside the mRNA approach, the US start-up Armora Biosciences is exploring a complementary avenue guided by the research of George Liu , who is also based in San Diego. At the heart of this is hyaluronidase, the enzyme that breaks down hyaluronic acid in the skin. The enzyme exists in two forms: one breaks it down into simple sugars, maintaining the balance of the tissues; the other breaks it down into large molecular blocks which the immune system interprets as a red alert. The key discovery is that C. acnes is not uniform: some strains secrete the protective variant, whilst others secrete the pro-inflammatory one. Armora’s vaccine aims to selectively neutralise this latter harmful variant, specifically targeting the reddest and most painful lesions.

The need for new therapeutic approaches stems from the limitations of current treatments. Oral isotretinoin is highly effective but is associated with significant adverse effects, whilst the systemic use of antibiotics is showing its limitations. ““We are well aware that prolonged use of antibiotics selects for bacterial resistance and alters the microbiome, which we now know to be at the heart of a great many diseases,” observes Longo. “It is no coincidence that the guidelines strictly limit the duration of treatment and discourage prolonged use as monotherapy,” he adds. Vaccines aim to block toxic proteins without destroying resident microorganisms, thereby preventing resistance. However, a degree of clinical caution remains necessary. “Acne is a complex, multifactorial condition arising from the convergence of four factors: androgenic stimulation with sebum overproduction, follicular hyperkeratinisation with comedone formation, skin microbiome dysbiosis and the resulting inflammatory response,” emphasises Longo. “The vaccine targets inflammation and microbial imbalance, not the other mechanisms. The clinical response may therefore vary from patient to patient depending on the predominant factor,” he concludes.