Needle-phobia? Scientists invent pain-free vaccine cream

Commentary by Dr. Donald Greig

Scientists believe the vaccination approach that doesn’t involve needles could enter clinical trials involving humans within two or three years

The prospect of a pain-free vaccine cream represents a significant advance in vaccination technology, particularly for individuals with needle phobia. Scientists are optimistic that clinical trials for such an innovative approach could begin within the next two to three years, potentially transforming the landscape of immunization.

Recent studies have investigated the role of Staphylococcus epidermidis, a common skin bacterium, in stimulating the immune response in laboratory mice. This research has demonstrated that these bacteria can elicit the production of antibodies against tetanus and diphtheria. The underlying mechanism involves sentinel cells within the skin, which periodically traverse the dermal layers, sampling proteins and other antigens. These sentinel cells play a crucial role in the immune system by presenting these samples to other immune cells, thereby initiating a tailored antibody response.

The current research builds on this foundation by utilizing modified forms of Staphylococcus epidermidis. Specifically, scientists have inserted a gene encoding a portion of the tetanus toxin into the AAP protein of the bacteria. This modification aims to trigger a more robust immune response against tetanus by directly exposing the immune system to a recognizable component of the toxin. Preliminary experiments have shown promising results, indicating that the immune systems of the mice can indeed recognize this modified antigen and produce specific antibodies.

This approach aligns with ongoing animal research, which seeks to understand how different immune systems react to novel forms of immunization. By leveraging the natural behavior of sentinel cells and the innate properties of skin-dwelling bacteria, researchers are exploring a novel pathway for vaccine delivery. This method not only targets the immune system effectively but also avoids the psychological barriers associated with needle injections.

In summary, the development of a needle-free vaccine cream is not merely a theoretical concept but is grounded in significant scientific research and experimentation. As scientists continue to explore the interactions between skin bacteria and the immune system, the potential for a pain-free vaccination method becomes increasingly tangible. If successful, this innovation could enhance vaccination rates and improve public health outcomes, particularly among populations that are hesitant or fearful of traditional needle-based immunizations.

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Article by: Rhys Blakely

Anyone who has a phobia of needles will welcome scientific research into creating pain-free vaccines that can be rubbed into the skin.

“We all hate needles — everybody does,” said Dr Michael Fischbach of Stanford University, who has led the research. “I haven’t found a single person who doesn’t like the idea that it’s possible to replace a shot with a cream.”

The breakthrough involves Staphylococcus epidermidis, a generally harmless species of bacteria that lives on human skin. “These bugs reside on every hair follicle of virtually every person on the planet,” Fischbach said.

His team began their work by exploring what happened when they added S. epidermidis to the skin of laboratory mice, where it isn’t naturally found. They saw that the rodents’ immune systems leapt into action. When they analysed the animals’ blood, it contained antibodies that had been produced to prevent S. epidermidis from infiltrating deeper into the rodents’ bodies.

In the research mice responded to the cream as though they had been vaccinated

Antibodies work by binding to specific parts of invading microbes, often preventing pathogens from entering cells and infections from worsening. Each antibody molecule typically targets a particular feature found on the surface of a specific microbial species or strain.

During the research the scientists witnessed that the mice had produced antibodies that bound to S. epidermidis. “It’s as if the mice had been vaccinated,” Fischbach said. “Their antibody response was just as strong and specific as if it had been reacting to a pathogen.”

Another set of experiments revealed that something similar occurs 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,” Fischbach said.

In a study published in the journal Nature, he and his colleagues describe how a particular part of S. epidermidis — a protein found on the surface of the bacteria, known as accumulation-associated protein (Aap) — was revealed to play a key role in provoking the immune response. Much larger than most proteins of its kind, it protrudes from the bacterial cell wall.

The researchers suspect that elements of the human and mouse immune systems known as “sentinel cells” periodically crawl through the skin, snatch samples of the prominent Aap and ferry them inside the body. These samples are shown to other immune cells, which then produce tailor-made antibodies.

The cream could be used for viruses, bacteria, fungi and one-celled parasites

For the final stage of the research, the scientists produced a modified version of the bacteria, with a gene that produces part of the tetanus toxin inserted into the Aap protein. They then ran an experiment to see whether the mice’s immune systems would “see” the tetanus and develop a specific antibody response to it.

Rodents that were swabbed with the bioengineered S. epidermidis developed extremely high levels of antibodies against the tetanus toxin. When the researchers then injected the animals with doses of tetanus toxin that would normally be lethal, the mice that had received the modified bacteria remained symptom-free, while those that had been swabbed with the original bacteria died.

In a similar experiment, the researchers snapped in the gene for diphtheria toxin instead of the one for tetanus toxin into the Aap protein and it also induced high antibody concentrations, this time targeting the diphtheria toxin.

The researchers also showed, by adding S. epidermidis to the skin of very young mice, the bacteria’s prior presence on the skin of these animals did not interfere with the experimental treatment’s ability to prompt a potent antibody response.

This implies that the fact that almost every human is naturally colonised by S. epidermidis should not be barrier to a modified version being used as a vaccine for people.

“We know it works in mice,” said Fischbach. “Next, we need to show it works in monkeys. That’s what we’re going to do.” If things go well, he expects to see this vaccination approach enter clinical trials involving humans within two or three years.

“We think this will work for viruses, bacteria, fungi and one-celled parasites,” he added. “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.”