A skin patch to treat peanut allergies teaches the body to tolerate the nuts
Ever since he was a baby, Sharon Wong’s son Brandon suffered from rashes, prolonged respiratory issues and vomiting. In 2006, as a young child, he was diagnosed with a severe peanut allergy.
"My son had a history of reacting to traces of peanuts in the air or in food,” says Wong, a food allergy advocate who runs a blog focusing on nut free recipes, cooking techniques and food allergy awareness. “Any participation in school activities, social events, or travel with his peanut allergy required a lot of preparation.”
Peanut allergies affect around a million children in the U.S. Most never outgrow the condition. The problem occurs when the immune system mistakenly views the proteins in peanuts as a threat and releases chemicals to counteract it. This can lead to digestive problems, hives and shortness of breath. For some, like Wong’s son, even exposure to trace amounts of peanuts could be life threatening. They go into anaphylactic shock and need to take a shot of adrenaline as soon as possible.
Typically, people with peanut allergies try to completely avoid them and carry an adrenaline autoinjector like an EpiPen in case of emergencies. This constant vigilance is very stressful, particularly for parents with young children.
“The search for a peanut allergy ‘cure’ has been a vigorous one,” says Claudia Gray, a pediatrician and allergist at Vincent Pallotti Hospital in Cape Town, South Africa. The closest thing to a solution so far, she says, is the process of desensitization, which exposes the patient to gradually increasing doses of peanut allergen to build up a tolerance. The most common type of desensitization is oral immunotherapy, where patients ingest small quantities of peanut powder. It has been effective but there is a risk of anaphylaxis since it involves swallowing the allergen.
"By the end of the trial, my son tolerated approximately 1.5 peanuts," Sharon Wong says.
DBV Technologies, a company based in Montrouge, France has created a skin patch to address this problem. The Viaskin Patch contains a much lower amount of peanut allergen than oral immunotherapy and delivers it through the skin to slowly increase tolerance. This decreases the risk of anaphylaxis.
Wong heard about the peanut patch and wanted her son to take part in an early phase 2 trial for 4-to-11-year-olds.
“We felt that participating in DBV’s peanut patch trial would give him the best chance at desensitization or at least increase his tolerance from a speck of peanut to a peanut,” Wong says. “The daily routine was quite simple, remove the old patch and then apply a new one. By the end of the trial, he tolerated approximately 1.5 peanuts.”
How it works
For DBV Technologies, it all began when pediatric gastroenterologist Pierre-Henri Benhamou teamed up with fellow professor of gastroenterology Christopher Dupont and his brother, engineer Bertrand Dupont. Together they created a more effective skin patch to detect when babies have allergies to cow's milk. Then they realized that the patch could actually be used to treat allergies by promoting tolerance. They decided to focus on peanut allergies first as the more dangerous.
The Viaskin patch utilizes the fact that the skin can promote tolerance to external stimuli. The skin is the body’s first defense. Controlling the extent of the immune response is crucial for the skin. So it has defense mechanisms against external stimuli and can promote tolerance.
The patch consists of an adhesive foam ring with a plastic film on top. A small amount of peanut protein is placed in the center. The adhesive ring is attached to the back of the patient's body. The peanut protein sits above the skin but does not directly touch it. As the patient sweats, water droplets on the inside of the film dissolve the peanut protein, which is then absorbed into the skin.
The peanut protein is then captured by skin cells called Langerhans cells. They play an important role in getting the immune system to tolerate certain external stimuli. Langerhans cells take the peanut protein to lymph nodes which activate T regulatory cells. T regulatory cells suppress the allergic response.
A different patch is applied to the skin every day to increase tolerance. It’s both easy to use and convenient.
“The DBV approach uses much smaller amounts than oral immunotherapy and works through the skin significantly reducing the risk of allergic reactions,” says Edwin H. Kim, the division chief of Pediatric Allergy and Immunology at the University of North Carolina, U.S., and one of the principal investigators of Viaskin’s clinical trials. “By not going through the mouth, the patch also avoids the taste and texture issues. Finally, the ability to apply a patch and immediately go about your day may be very attractive to very busy patients and families.”
Brandon Wong displaying origami figures he folded at an Origami Convention in 2022
Sharon Wong
Clinical trials
Results from DBV's phase 3 trial in children ages 1 to 3 show its potential. For a positive result, patients who could not tolerate 10 milligrams or less of peanut protein had to be able to manage 300 mg or more after 12 months. Toddlers who could already tolerate more than 10 mg needed to be able to manage 1000 mg or more. In the end, 67 percent of subjects using the Viaskin patch met the target as compared to 33 percent of patients taking the placebo dose.
“The Viaskin peanut patch has been studied in several clinical trials to date with promising results,” says Suzanne M. Barshow, assistant professor of medicine in allergy and asthma research at Stanford University School of Medicine in the U.S. “The data shows that it is safe and well-tolerated. Compared to oral immunotherapy, treatment with the patch results in fewer side effects but appears to be less effective in achieving desensitization.”
The primary reason the patch is less potent is that oral immunotherapy uses a larger amount of the allergen. Additionally, absorption of the peanut protein into the skin could be erratic.
Gray also highlights that there is some tradeoff between risk and efficacy.
“The peanut patch is an exciting advance but not as effective as the oral route,” Gray says. “For those patients who are very sensitive to orally ingested peanut in oral immunotherapy or have an aversion to oral peanut, it has a use. So, essentially, the form of immunotherapy will have to be tailored to each patient.” Having different forms such as the Viaskin patch which is applied to the skin or pills that patients can swallow or dissolve under the tongue is helpful.
The hope is that the patch’s efficacy will increase over time. The team is currently running a follow-up trial, where the same patients continue using the patch.
“It is a very important study to show whether the benefit achieved after 12 months on the patch stays stable or hopefully continues to grow with longer duration,” says Kim, who is an investigator in this follow-up trial.
"My son now attends university in Massachusetts, lives on-campus, and eats dorm food. He has so much more freedom," Wong says.
The team is further ahead in the phase 3 follow-up trial for 4-to-11-year-olds. The initial phase 3 trial was not as successful as the trial for kids between one and three. The patch enabled patients to tolerate more peanuts but there was not a significant enough difference compared to the placebo group to be definitive. The follow-up trial showed greater potency. It suggests that the longer patients are on the patch, the stronger its effects.
They’re also testing if making the patch bigger, changing the shape and extending the minimum time it’s worn can improve its benefits in a trial for a new group of 4-to-11 year-olds.
The future
DBV Technologies is using the skin patch to treat cow’s milk allergies in children ages 1 to 17. They’re currently in phase 2 trials.
As for the peanut allergy trials in toddlers, the hope is to see more efficacy soon.
For Wong’s son who took part in the earlier phase 2 trial for 4-to-11-year-olds, the patch has transformed his life.
“My son continues to maintain his peanut tolerance and is not affected by peanut dust in the air or cross-contact,” Wong says. ”He attends university in Massachusetts, lives on-campus, and eats dorm food. He still carries an EpiPen but has so much more freedom than before his clinical trial. We will always be grateful.”
What to Know about the Fast-Spreading Delta Variant
A highly contagious form of the coronavirus known as the Delta variant is spreading rapidly and becoming increasingly prevalent around the world. First identified in India in December, Delta has now been identified in 111 countries.
In the United States, the variant now accounts for 83% of sequenced COVID-19 cases, said Rochelle Walensky, director of the Centers for Disease Control and Prevention, at a July 20 Senate hearing. In May, Delta was responsible for just 3% of U.S. cases. The World Health Organization projects that Delta will become the dominant variant globally over the coming months.
So, how worried should you be about the Delta variant? We asked experts some common questions about Delta.
What is a variant?
To understand Delta, it's helpful to first understand what a variant is. When a virus infects a person, it gets into your cells and makes a copy of its genome so it can replicate and spread throughout your body.
In the process of making new copies of itself, the virus can make a mistake in its genetic code. Because viruses are replicating all the time, these mistakes — also called mutations — happen pretty often. A new variant emerges when a virus acquires one or more new mutations and starts spreading within a population.
There are thousands of SARS-CoV-2 variants, but most of them don't substantially change the way the virus behaves. The variants that scientists are most interested in are known as variants of concern. These are versions of the virus with mutations that allow the virus to spread more easily, evade vaccines, or cause more severe disease.
"The vast majority of the mutations that have accumulated in SARS-CoV-2 don't change the biology as far as we're concerned," said Jennifer Surtees, a biochemist at the University of Buffalo who's studying the coronavirus. "But there have been a handful of key mutations and combinations of mutations that have led to what we're now calling variants of concern."
One of those variants of concern is Delta, which is now driving many new COVID-19 infections.
Why is the Delta variant so concerning?
"The reason why the Delta variant is concerning is because it's causing an increase in transmission," said Alba Grifoni, an infectious disease researcher at the La Jolla Institute for Immunology. "The virus is spreading faster and people — particularly those who are not vaccinated yet — are more prone to exposure."
The Delta variant has a few key mutations that make it better at attaching to our cells and evading the neutralizing antibodies in our immune system. These mutations have changed the virus enough to make it more than twice as contagious as the original SARS-CoV-2 virus that emerged in Wuhan and about 50% more contagious than the Alpha variant, previously known as B.1.1.7, or the U.K. variant.
These mutations were previously seen in other variants on their own, but it's their combination that makes Delta so much more infectious.
Do vaccines work against the Delta variant?
The good news is, the COVID-19 vaccines made by AstraZeneca, Johnson & Johnson, Moderna, and Pfizer still work against the Delta variant. They remain more than 90% effective at preventing hospitalizations and death due to Delta. While they're slightly less protective against disease symptoms, they're still very effective at preventing severe illness caused by the Delta variant.
"They're not as good as they were against the prior strains, but they're holding up pretty well," said Eric Topol, a physician and director of the Scripps Translational Research Institute, during a July 19 briefing for journalists.
Because Delta is better at evading our immune systems, it's likely causing more breakthrough infections — COVID-19 cases in people who are vaccinated. However, breakthrough infections were expected before the Delta variant became widespread. No vaccine is 100% effective, so breakthrough infections can happen with other vaccines as well. Experts say the COVID-19 vaccines are still working as expected, even if breakthrough infections occur. The majority of these infections are asymptomatic or cause only mild symptoms.
Should vaccinated people worry about the Delta variant?
Vaccines train our immune systems to protect us against infection. They do this by spurring the production of antibodies, which stick around in our bodies to help fight off a particular pathogen in case we ever come into contact with it.
But even if the new Delta variant slips past our neutralizing antibodies, there's another component of our immune system that can help overtake the virus: T cells. Studies are showing that the COVID-19 vaccines also galvanize T cells, which help limit disease severity in people who have been vaccinated.
"While antibodies block the virus and prevent the virus from infecting cells, T cells are able to attack cells that have already been infected," Grifoni said. In other words, T cells can prevent the infection from spreading to more places in the body. A study published July 1 by Grifoni and her colleagues found that T cells were still able to recognize mutated forms of the virus — further evidence that our current vaccines are effective against Delta.
Can fully vaccinated people spread the Delta variant?
Previously, scientists believed it was unlikely for fully vaccinated individuals with asymptomatic infections to spread Covid-19. But the Delta variant causes the virus to make so many more copies of itself inside the body, and high viral loads have been found in the respiratory tracts of people who are fully vaccinated. This suggests that vaccinated people may be able to spread the Delta variant to some degree.
If you have COVID-19 symptoms, even if you're fully vaccinated, you should get tested and isolate from friends and family because you could spread the virus.
What risk does Delta pose to unvaccinated people?
The Delta variant is behind a surge in cases in communities with low vaccination rates, and unvaccinated Americans currently account for 97% of hospitalizations due to COVID-19, according to Walensky. The best thing you can do right now to prevent yourself from getting sick is to get vaccinated.
Gigi Gronvall, an immunologist and senior scholar at the Johns Hopkins Center for Health Security, said in this week's "Making Sense of Science" podcast that it's especially important to get all required doses of the vaccine in order to have the best protection against the Delta variant. "Even if it's been more than the allotted time that you were told to come back and get the second, there's no time like the present," she said.
With more than 3.6 billion COVID-19 doses administered globally, the vaccines have been shown to be incredibly safe. Serious adverse effects are rare, although scientists continue to monitor for them.
Being vaccinated also helps prevent the emergence of new and potentially more dangerous variants. Viruses need to infect people in order to replicate, and variants emerge because the virus continues to infect more people. More infections create more opportunities for the virus to acquire new mutations.
Surtees and others worry about a scenario in which a new variant emerges that's even more transmissible or resistant to vaccines. "This is our window of opportunity to try to get as many people vaccinated as possible and get people protected so that so that the virus doesn't evolve to be even better at infecting people," she said.
Does Delta cause more severe disease?
While hospitalizations and deaths from COVID-19 are increasing again, it's not yet clear whether Delta causes more severe illness than previous strains.
How can we protect unvaccinated children from the Delta variant?
With children 12 and under not yet eligible for the COVID-19 vaccine, kids are especially vulnerable to the Delta variant. One way to protect unvaccinated children is for parents and other close family members to get vaccinated.
It's also a good idea to keep masks handy when going out in public places. Due to risk Delta poses, the American Academy of Pediatrics issued new guidelines July 19 recommending that all staff and students over age 2 wear face masks in school this fall, even if they have been vaccinated.
Parents should also avoid taking their unvaccinated children to crowded, indoor locations and make sure their kids are practicing good hand-washing hygiene. For children younger than 2, limit visits with friends and family members who are unvaccinated or whose vaccination status is unknown and keep up social distancing practices while in public.
While there's no evidence yet that Delta increases disease severity in children, parents should be mindful that in some rare cases, kids can get a severe form of the disease.
"We're seeing more children getting sick and we're seeing some of them get very sick," Surtees said. "Those children can then pass on the virus to other individuals, including people who are immunocompromised or unvaccinated."
New Podcast: Dr. Gigi Gronvall Addresses the Risk of Delta and COVID-19’s Possible Origins
"Making Sense of Science" is a monthly podcast that features interviews with leading medical and scientific experts about the latest developments and the big ethical and societal questions they raise. This episode is hosted by science and biotech journalist Emily Mullin, summer editor of the award-winning science outlet Leaps.org.