The finding could lead to the development of needle-free vaccines.

• Giorgia Guglielmi

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Skin can generate antibodies, independent of the rest of the immune system.Credit: kazuma seki/Getty

The skin — once thought to be a mainly passive barrier — can produce its own antibodies that fight off infections, a pair of studies reports in Nature this week1,2. The findings could pave the way for the development of needle-free vaccines that can be applied to the skin.

Although scientists have previously seen immune responses in the skin during infections, finding similar reactions in healthy skin is “a surprise”, says Daniel Kaplan, a dermatologist and immunologist at the University of Pittsburgh in Pennsylvania. “The idea of a semi-autonomous immune system in a peripheral tissue is very exciting,” he says.

Dual role

The immune system has to fight off harmful pathogens without attacking the helpful microorganisms that inhabit the body. Previous research showed3 that the skin of adult mice that had been raised without microbes could be colonized by Staphylococcus epidermidis, a common and harmless bacterium found on human skin. This long-term colonization triggered the production of specific immune cells, called T cells, which helped to strengthen local immunity.

“The next and maybe main chapter in this saga is that the response to this ubiquitous skin colonist is much more potent than we had realized,” says Michael Fischbach, a microbiologist at Stanford University in California, who co-authored both of the latest studies. 

“When the immune system sees a friendly bacterium, you would think that it would just give a friendly wave and walk in the other direction, but that’s not at all what happens,” he says.

In experiments with mice, Fischbach and his colleagues discovered that S. epidermidis triggers the activation of B cells, the immune cells necessary to produce antibodies1. The skin then made antibodies against S. epidermidis; these persisted for at least 200 days and could form without previous exposure to other microbes.

The skin was able to generate this immune response even when lymph nodes — the immune hubs that help to activate immune cells — were disabled. The presence of S. epidermidis also induced the formation of specialized immune structures in the skin that attract T and B cells, boosting the production of antibodies.

Immune memory

Vaccines work by teaching the immune system — which includes T and B cells, along with antibodies — to recognize and remember a pathogen, so the body can respond quickly if exposed again.

Building on this idea, Fischbach and his team explored whether they could redirect the immune response triggered by the harmless S. epidermidis to target pathogens, to develop a new type of vaccine.

In a second study2, the researchers showed that S. epidermidis triggers an antibody response resembling that seen in conventional vaccines.

By modifying S. epidermidis to display foreign proteins — such as part of the tetanus toxin — on its surface, the researchers were able to induce immune responses in the mice’s bloodstream and in mucous membranes such as the lining of the nose. These responses protected the animals when they were given a lethal dose of the toxin.

Mucosal vaccines

Fischbach’s work is part of a growing interest in developing vaccines that induce antibodies in mucosal areas. This type of protection could help to stop respiratory or other infections before they start and reduce the spread of disease.

Another advantage over conventional vaccines is that engineered S. epidermidis could be added to a cream and simply applied to the skin. Such a vaccine, Fischbach says, would be cheap to produce and easy to distribute. Furthermore, it would not have to be administered by health-care worker, making it especially useful in under-served regions of the world.

The idea of using the immune response from S. epidermidis in the skin to develop therapies “is really out there”, says Thomas Kupper, a skin immunologist at Harvard Medical School in Boston, Massachusetts. “It is a super-creative application of these findings.”

But Kupper adds that it’s still unclear whether the skin’s response to S. epidermidis is as strong in people as it is in mice. Fischbach notes that early data suggest healthy people have high levels of antibodies against S. epidermidis. But before this approach can be used in people, it must first be proved safe and effective in non-human primates and in humans, following the usual process for developing medicines, he says. “If this is going to be deployed in the real world, we have to show that it works.”

doi: https://doi.org/10.1038/d41586-024-04068-9

References

1. Gribonika, I. et al. Nature https://doi.org/10.1038/s41586-024-08376-y (2024).Article Google Scholar 
2. Bousbaine, D. et al. Nature https://doi.org/10.1038/s41586-024-08489-4 (2024).Article Google Scholar 
3. Naik, S. et al. Nature 520, 104–108 (2015).Article PubMed Google Scholar 

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