Scientists have come up with a nasal spray “vaccine” that appears to redirect or potentially reverse the allergic response to peanuts.
So far, the therapy has only been tested in animal models, so whether it will work in humans is a big question. But results in mice showed that three monthly doses could basically reprogram the immune system and protect against allergic reactions even in mice that were already allergic to peanuts.
“We’re changing the way the immune cells respond upon exposure to allergens,” lead Jessica O’Konek, PhD, the Mary H. Weiser Food Allergy Center at the University of Michigan, Ann Arbor, said in a press release. “Importantly, we can do this after allergy is established, which provides for potential therapy of allergies in humans.”
O’Konek and colleagues published their results online April 11 in the Journal of Allergy and Clinical Immunology.
Despite the rising incidence of food allergies, there are currently no approved therapies to prevent allergic reactions. Most efforts thus far have focused on developing allergen-specific immunotherapies, which rely on exposure to increasing doses of the allergen. However, the approach has significant drawbacks: it doesn’t work for everyone, the effect appears to fade quickly after therapy cessation, and it can trigger serious reactions, including anaphylaxis.
Therefore, scientists are searching for allergy treatments that are more long-lasting and safer than immunotherapy.
O’Konek and colleagues developed a vaccine containing peanut extract and a new type of adjuvant, which they called a “nanoemulsion.” Past work by this group suggested the nanoemulsion can redirect the immune system away from TH2 responses, which are overactive in allergies, toward TH1 and TH17 responses, which are implicated in protective immunity. (TH1 and TH17 responses are also associated with autoimmunity when they go on overdrive).
The researchers tested the vaccine in two different mouse models sensitized to peanuts. The mice were treated with 3 monthly intranasal doses of either peanut extract plus the nanoemulsion or peanut extract plus saline.
After treatment, the mice that received the nanoemoulsion vaccine had a 10-fold lower level of peanut-specific immunoglobulin E than those treated with saline.
Two and 4 weeks after the last dose, mice that received the nasal therapy had decreased TH2 responses and increased TH1 and TH17 responses.
Mice that received the vaccine therapy also showed significantly decreased allergic responses in response to a peanut oral challenge. In contrast, control animals who had received intranasal peanut in saline instead of the “vaccine” showed no change in their allergic responses, including pruritus, puffiness around the eyes and mouth, piloerection, and wheezing.
Further experiments showed that mice immunized with the nanoemulsion vaccine were less likely to experience severe reactions such as anaphylaxis in response to peanut extract delivered via intraperitoneal injection.
The authors note that longer studies are underway to determine how long protection lasts in mice. In addition, further studies are needed in mice to understand the mechanisms involved.
Although the results look promising, this is only one approach among several in the early stages of development, Brian Vickery, MD, director of the Food Allergy Center at Emory+Children’s Hospital, Atlanta, Georgia, told Medscape Medical News.
One major issue, he said, is that food allergy research is plagued by animal models that do not replicate human disease very well. Although the mouse models used in the study may be as good as any currently available, results in mice may not translate well to humans.
“There is plenty of precedent for really beautiful-looking preclinical animal data that do not translate well when the same approach is studied in humans,” Vickery said.
He said at least two past studies that used similar mouse models as the one in the study by O’Konek and colleagues come to mind. The first tested a combination of Chinese herbs that appeared to enhance the TH1 response and reverse the TH2 response. The second involved a recombinant DNA product intended to produce a safer form of immunotherapy. In both studies, results in mice looked very promising, but when the treatments were tested in humans with peanut allergies, they either did not work or produced unacceptable reactions.
Yet Vickery sees reason for “cautious optimism.”
“There have been other programs that have generated data that frankly weren’t even quite this good and that have moved to humans. From that standard, it would be reasonable to proceed to human trials,” he said.
Research in this field currently remains in the early stages, but the approach by O’Konek and colleagues is in line with other efforts. “The field is moving to next-generation therapies. This study is a step in the right direction, but all of this is very early stage. To say that a peanut allergy vaccine reverses the problem and solves it is not representative of where the field is at right now.”
The study was funded by the US Department of Defense, Food Allergy Research & Education, and a gift from the Shaevsky family. One or more authors reports grants from one or more of the following: Food Allergy Research & Education, US Department of Defense, and the Shaevsky Family. O’Konek and coauthor Baker have a patent pending. Baker is chief executive officer and chief marketing officer of Food Allergy Research & Education. Vickery is a former employee of Aimm Therapeutics, which works on antibody-based treatments against cancer and infectious disease.
J Allergy Clin Immunol. Published online March 13, 2018. Abstract
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