"Vaccine" applied on the skin? Skin commensal bacteria are expected to bring a new breakthrough in painless vaccination!

Skin is more than just a barrier

Skin is the largest organ in our body. It is not only a barrier to protect us from external harm, but also an active micro-ecosystem. In this vast "surface kingdom", the microbial community is thriving, among which Staphylococcus epidermidis plays a key role. We know that there are hundreds of millions of microorganisms living on the skin, which are often called "skin microbiota" or "skin symbiotic microorganisms". Among them, Staphylococcus epidermidis is the most common resident. Most of the time, these residents coexist with us and jointly maintain the ecological balance of the skin.

Recently, a paper in Nature revealed an amazing discovery: Staphylococcus epidermidis can induce the human body to produce a long-lasting and accurate antibody response. This natural immune mechanism is not only beneficial to the health of the skin, but may also become an important breakthrough for future vaccines and non-invasive treatments. Common Staphylococcus epidermidis can not only affect the immune system on the skin, but can also be used as a vaccine carrier through "transformation" to fight other pathogenic microorganisms. This discovery may change the way vaccines are developed, thus bringing about a new type of "smear-type vaccine."

1. Skin probiotics: Symbiotic microorganisms in the body

1. Introduction to Staphylococcus epidermidis

Staphylococcus epidermidis is a common skin microbe that occupies an important part of our skin microbiome. Although its name may remind us of the pathogen "Staphylococcus aureus", in fact, this "neighbor" is more often a "protector" on the skin.

Staphylococcus epidermidis can help maintain the skin barrier and inhibit the overgrowth of harmful pathogens. It can play an important role in health and disease by interacting with the host immune system and regulating immunity.

2. Findings from the Nature paper

The research team found that Staphylococcus epidermidis not only survives on the surface of the skin, but also "communicates" with the immune system at a deep level. This communication can produce a strong antibody response that is long-lasting and specific, indicating that the human body has long evolved a mechanism that uses skin microorganisms as a "natural instructor" for immune training.

2. How does Staphylococcus epidermidis activate the immune system?

1. Antibody response to Aap protein

The researchers focused on a cell surface protein of Staphylococcus epidermidis called Aap (accumulation-associated protein). They found that Aap was the main target of antibody responses in humans and primates. This protein helps the bacteria attach to the skin and is also a key to the immune system's recognition and attack.

2. Coordinated T and B cell responses

Surprisingly, this antibody response depends not only on the memory of immune B cells, but also on the synergy of immune T cells. This mechanism of immune response is called "co-activation", which not only enhances the persistence of antibody response, but also provides a new direction for future vaccine design.

[Note: The image is from this paper. (The immunogenicity and protective evaluation of Aap-sc-TTFC in mice showed that the modified strain was applied to the mouse skin to simulate the natural colonization process. The study found that the mice produced high titers of anti-TTFC IgG antibodies.)]

3. Inspiration: From skin to vaccine, and then to smearable "vaccine"

1. Spread-on “vaccines” inspired by natural immunity

Research has shown that Staphylococcus epidermidis on the skin can not only trigger an antibody response, but can also be modified to express specific antigenic proteins, redirecting the immune system to fight specific pathogens. In simple terms, this mechanism is similar to vaccination, and it also provides new possibilities for non-invasive smear-type "vaccine" vaccination.

We know that non-invasive vaccination is a type of vaccination that can be done without injections, through simple smearing or chip patches. This method of customizing Staphylococcus epidermidis on the skin can deliver therapeutic proteins or antigens directly to specific areas by modifying the carrier of probiotics and reducing overall side effects.

2. Other potential applications, such as

Treatment of skin diseases: such as eczema, psoriasis, etc., by re-regulating the skin's microecological structure and restoring the overall healthy immune balance of the skin.

Tumor immunotherapy: Using modified Staphylococcus epidermidis can act as a Trojan horse to deliver antigens to the skin and modulate systemic immune responses.

IV. Future Challenges and Prospects

While this discovery is exciting, several challenges still need to be addressed, such as:

Ⅰ. Safety: How to ensure that the modified Staphylococcus epidermidis will not cause other infections or side effects?

II. Broad Applicability: Do the immune systems of different populations respond consistently to S. epidermidis?

III. Regulations and ethics: The development of probiotic vaccines must comply with strict medical and ethical standards.

Regardless, the research does open up a new path for future vaccines and treatments.

Finally: A new chapter in skin microecology

From the "guardian" of the skin to the "vaccine carrier" of the future, Staphylococcus epidermidis is also redefining our understanding of skin probiotics. This study not only reveals the complex relationship between natural microorganisms and the immune system, but also provides a new hope for non-invasive vaccines and individual precision medicine.

Perhaps, the next time we talk about skin, we can no longer regard it as a simple barrier, but as a comprehensive "immune training ground", an approach that may bring revolutionary changes in the field of health.

References

Discovery and engineering of the antibody response to a prominent skin commensal. Nature, 2024. DOI:10.1038/s41586-024-08489-4