Could getting a vaccine one day be as simple as applying an inexpensive skin cream? New research reported in Nature has suggested that yes, that possibility could be reality, and within only a few years. “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, a Professor at Stanford.
Staphylococcus epidermis is a microbe that loves to live on human skin. These bacteria are generally harmless and live on most everyone's hair follicles, Fischbach said. But the immune system also mounts an aggressive response against S. epidermis by generating antibodies, which can neutralize pathogens, and are often specialized to react specifically against one in particular. Fischbach and colleagues have now taken advantage of the antibody-generating aspect of that immune response against S epidermis.
The researchers found that mice that do not usually carry S. epidermis will generate anti-S epidermis antibodies when exposed to the microbe. After starting off slowly, that antibody production eventually reached levels that were higher than anyone anticipated, and even exceeded those generated by a regular vaccine. They also remained high, and the antibodies were just as specific as they would be against a pathogen. “It’s as if the mice had been vaccinated,” Fischbach said.
The scientists then determined that similar processes are at naturally also at work humans. “We got blood from human donors and found that their circulating levels of antibodies directed at S. epidermis were as high as anything we get routinely vaccinated against.”
This was surprising, since the skin is considered to be a major part of the immune system as it acts as a massive physical barrier against pathogens. But it apparently needs the help of the immune system to be truly effective.
These antibodies help the immune system protect us from cuts and scratches that we often get during daily life, Fischbach said. The S. epidermis response also seems to be preemptive, so the immune system is then freed from monitoring this situation constantly, and can respond to other invaders instead.
The investigators set about modifying S. epidermis into a live vaccine that could be applied topically. They first determined that a molecule called Aap is the part of S. epidermis that triggers the strongest immune response. Aap causes the levels of antibodies known as IgG and IgA to increase.
The researchers then added a portion of tetanus toxin to Aap, and repeated the experiment in which mice were exposed to the germ. The mice exposed to engineered Aap did indeed develop antibodies against tetanus toxin. When these mice were then given lethal tetanus toxin levels, they did not develop any symptoms. Control mice did not respond this way, and were killed by the toxin.
This work was repeated for diphtheria toxin to similar effect. The researchers also found that two or three applications of the modified bacteria could induce sufficient immune responses in the mice.
The work also showed that natural colonization with S. epidermis dies not interfere with this process, in a mouse model.
Now the researchers are planning additional pre-clinical trials. Positive results may lead to clinical trials, potentially in about three years, suggested Fischbach.
“We think this will work for viruses, bacteria, fungi and one-celled parasites,” he 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.”
Sources: Stanford University, Nature