Working with a bacterium that lives on human skin, Stanford Medicine scientists created a topical vaccine that protected mice against tetanus.
Bacteria lab photo: Gregory Strout, photo of swab: jmsilva via Getty Images, photo illustration: Emily Moskal
A painless future of vaccination could be on the horizon, as researchers have been working on innovative delivery methods.
Stanford University scientists have now presented another unique method using a common skin bacterium, Staphylococcus epidermidis.
They have advanced vaccination by transforming this bacterium into a painless, skin-applied topical vaccine.
This technology could lead to a future where vaccines could be simply rubbed onto the skin like creams. This would eliminate the need for needles as well as reduce side effects like fever and soreness.
This approach could also make vaccinations more accessible and affordable.
“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,” said Michael Fischbach, PhD, the Liu (Liao) Family Professor and a professor of bioengineering.
Use of common skin bacteria
Some bacteria, like harmless Staphylococcus epidermidis, have adapted to thrive on human skin.
Immunologists have often overlooked the role of skin bacteria in our health. However, recent research suggests that this seemingly ordinary bacterium triggers a powerful immune response in our bodies.
The researchers wanted to know if a mouse, which doesn’t naturally have S. epidermidis on its skin, would produce antibodies against this bacteria if it were introduced.
Antibodies are specialized proteins that target specific invaders like bacteria and viruses.
In an experiment, the researchers applied S. epidermidis to the skin of mice and then monitored their blood for antibodies against the bacteria over six weeks.
Fischbach said. “Those antibodies’ levels increased slowly, then some more — and then even more. It’s as if the mice had been vaccinated.”
Interestingly, the antibody response was as robust and precise as if the bacteria were a harmful pathogen.
“The same thing appears to be occurring naturally in humans,” Fischbach said. “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.”
Bacteria use specific protien
The researchers identified a specific protein, Aap, on the surface of this bacteria that triggers a strong immune response.
The Aap protein — a large, tree-like structure — extends from the bacteria’s surface.
This protein’s structure allows it to interact with immune cells, prompting them to produce antibodies against the bacteria.
The Aap protein triggers the production of two main types of antibodies: IgG and IgA. IgG circulates in the bloodstream, while IgA antibodies protect the mucosal surfaces of the nose and lungs.
“We’re eliciting IgA in mice’s nostrils. Respiratory pathogens responsible for the common cold, flu and COVID-19 tend to get inside our bodies through our nostrils. Normal vaccines can’t prevent this. They go to work only once the pathogen gets into the blood. It would be much better to stop it from getting in in the first place,” Fischbach explained.
The researchers modified the Aap protein to display a harmless piece of tetanus toxin. They wanted to see if this modification would trigger an immune response and the production of antibodies against tetanus.
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The team conducted a dip-then-swab experiment. They compared the effects of the unmodified S. epidermidis with the genetically engineered version carrying the tetanus toxin fragment.
The mice treated with the modified bacteria developed high levels of antibodies against tetanus toxin. When these mice were exposed to a lethal dose of the toxin, they remained unaffected, while the untreated mice died.
As per the press release, the researchers discovered that just a few applications were sufficient to induce a protective immune response.
“We know it works in mice,” Fischbach said. “Next, we need to show it works in monkeys. That’s what we’re going to do.”
The findings were published in the journal Nature.
