The skin – once considered primarily a passive barrier – can produce its own antibodies that fight off infections, two studies report Nature this week^1,2. The findings could pave the way for the development of needle-free vaccines that can be applied to the skin.

Although scientists have observed immune reactions in the skin during infections before, 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 must fight harmful pathogens without attacking the helpful microorganisms in the body. Previous research showed³ that the skin of adult mice that were raised without microbes could be colonized by them Staphylococcus epidermidisa common and harmless bacterium found on human skin. This long-term colonization triggered the production of specific immune cells called T cells, which helped strengthen local immunity.

“The next and perhaps most important chapter in this saga is that the response to this ubiquitous skin colonist is much stronger than we thought,” 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 bacteria, you might think it would just wave friendly and go the other way, but that doesn’t happen at all,” he says.

Fischbach and his colleagues found this out in experiments with mice S. epidermidis triggers the activation of B cells, the immune cells necessary to produce antibodies¹. The skin then produced antibodies against it S. epidermidis; These persisted for at least 200 days and were able to form without first being exposed to other microbes.

The skin was able to produce this immune response even when lymph nodes – the immune centers that help activate immune cells – were deactivated. The presence of S. epidermidis It also induces the formation of specialized immune structures in the skin that attract T and B cells and thus increase the production of antibodies.

Immune memory

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

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

In a second study²That’s what the researchers showed S. epidermidis triggers an antibody response similar to that seen with traditional vaccines.

By modification S. epidermidis In order to make foreign proteins – such as part of the tetanus toxin – visible on its surface, the researchers were able to trigger immune reactions in the mice’s bloodstream and in mucous membranes such as the nasal mucosa. These reactions 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 stop respiratory or other infections before they occur and limit the spread of disease.

Another advantage over conventional vaccines is that they are technically manufactured S. epidermidis could be added to a cream and simply applied to the skin. Such a vaccine, says Fischbach, would be cheap to produce and easy to distribute. Additionally, it would not need to be administered by medical personnel, making it particularly useful in underserved regions of the world.

The idea of ​​using the immune response 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’s a super creative application of these insights.”

However, Kupper adds that it is still unclear whether the skin reacts to it S. epidermidis is just as strong in humans as it is in mice. Fischbach points out that initial data suggests that healthy people have high antibody levels S. epidermidis. But before this approach can be used in humans, it must first be proven to be safe and effective in nonhuman primates and in humans, following standard drug development procedures, he says. “If this is going to be implemented in the real world, we need to show that it works.”