Topical Cream Vaccine Created by Stanford University Scientists

• by Rishma Parpia

• Published December 22, 2024
• Vaccines

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A new study conducted by Stanford University scientists and published in Nature discusses a newly developed topical vaccine using Staphylococcus epidermidis, a common bacterium found on human skin. The researchers speculate that this new type of vaccine delivery system could offer  an alternative to traditional needle-based vaccinations  and avoid common side effects like fever, swelling, and soreness.¹

Michael Fischbach, PhD, professor of bioengineering at Stanford University and a researcher on the study stated:

We all hate needles—everybody does. I haven’t found a single person who doesn’t like the idea that it’s possible to replace a shot with a cream.”²

The study explored the use of S. epidermidis, a bacterium that lives on the skin of human beings. Although previously overlooked in immunology, recent findings indicate that S. epidermidis triggers a strong immune response when introduced to the body. In experiments with mice, the researchers applied the bacterium to the animals’ skin and measured the resulting immune response. The antibody levels produced were unexpectedly high, even surpassing those seen with conventional vaccines. “Those antibodies’ levels increased slowly, then some more—and then even more. It’s as if the mice had been vaccinated,” Dr. Fischback said.³

The researchers said that immunologists may have overlooked skin-colonizing bacteria because they were traditionally believed to have little impact on our health. They pointed outthat this discovery challenges prior assumptions about the bacteria, suggesting it could serve as a potential basis for vaccine development.^{4 5}

Fischbach added:

The same thing appears to be occurring naturally in humans. We got blood from human donors and found that their circulating levels of antibodies directed at S. epidermidis were as high as anything we get routinely vaccinated against.”⁶

Fischback found it puzzling that the immune system mounts such a strong response to bacteria like S. epidermidis, which reside on the skin’s surface without causing harm. “It seems as though our immune system’s reaction to these bacteria, hanging out beyond the skin’s antimicrobial barrier, serves no clear purpose,” he said.⁷

This raises the question: why does the immune system respond so vigorously? Fischbach likened it to the saying by poet Robert Frost… “Good fences make good neighbors,” explaining that many people assume the skin acts as a perfect barrier. However, he argues that the skin is far from impenetrable. Without the immune system’s assistance, it would quickly be compromised.⁸ He explained:

The best fence is those antibodies. They’re the immune system’s way of protecting us from the inevitable cuts, scrapes, nicks and scratches we accumulate in our daily existence.⁹

The immune system typically begins to produce antibodies only after a pathogen that causes disease has entered the body. In contrast, the response to S. epidermidis is proactive, occurring before any issue arises. This allows the immune system to be prepared in case of injury, such as a skin break, when the bacteria might enter the body and potentially spread through the bloodstream.¹⁰

Role of Aap Protein and Experimental Results

The researchers said the key factor in the success of their research is the Aap protein, which is found on the surface of S. epidermidis. This protein plays a critical role in stimulating immune cells to produce antibodies. Aap has a treelike structure that allows it to interact with immune cells and trigger the production of IgG and IgA antibodies. IgG antibodies circulate in the bloodstream, while IgA antibodies protect the mucosal surfaces, such as the nose and lungs, from pathogens.¹¹

To further test the potential of this approach, the researchers modified S. epidermidis to display a fragment of tetanus toxin using the Aap protein. The modified bacteria were applied to the skin of mice, and over several weeks, the animals developed specific antibody responses targeting the tetanus toxin. When the mice were later exposed to a lethal dose of tetanus toxin, the treated animals were protected, while the control group that received the unmodified bacteria did not survive.

This experiment demonstrated that the engineered bacteria could effectively function as a vaccine. The researchers found that only a few applications of the topical treatment were necessary to elicit a protective immune response.¹²

Future Implications

The research team believes their topical vaccine technology could extend beyond tetanus, potentially providing a new way to vaccinate against various viruses, bacteria, fungi, and parasites. They added that key advantage of this approach is that it seems to avoid the inflammatory responses commonly triggered by traditional vaccines, which can cause mild discomfort or side effects. Fischbach said:

Most vaccines have ingredients that stimulate an inflammatory response and make you feel a little sick. These bugs don’t do that. We expect that you wouldn’t experience any inflammation at all.¹³

Although the results in mice are promising, further studies are needed to evaluate the vaccine’s safety and effectiveness in humans. The team plans to conduct additional research in monkeys and anticipates beginning clinical trials within two to three years.¹⁴

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