Approximately 40% of the European population is allergic to pollen, and their symptoms cause the estimated loss of 100 million school and work days every year. Traditional treatment is allergen-specific immunotherapy (AIT), through which individuals are exposed to gradually increasing doses of the allergen until they become desensitized. However, this approach doesn’t work for all patients.
As proof-of-principle, researchers headed by a team at the International Center for Vaccinology, Kazakh National Agrarian Research University (KazNARU), engineered a monoclonal antibody (mAb) from mice that, when applied to the inside of the nose of mice sensitized to mugwort (Artemesia vulgaris) pollen, stopped the animals from developing hay fever and asthma symptoms in response to mugwort pollen challenge.
“This is the first time a monoclonal antibody designed to block a specific pollen allergen has been delivered directly into the nose, and been shown to protect against allergy symptoms in the upper and lower airways,” said Kaissar Tabynov, PhD, KazNARU director.
“In the future, similar antibodies could be developed for other major pollen allergens, such as ragweed or grass,” Tabynov suggested. “This opens the door to a new generation of precision allergy treatments that are fast-acting, needle-free, and tailored to individual allergen sensitivities.” Tabynov is senior author of the researchers’ published paper in Frontiers in Immunology, titled “Intranasal Monoclonal Antibodies to Mugwort Pollen Reduce Allergic Inflammation in a Mouse Model of Allergic Rhinitis and Asthma.” In their report, the authors wrote, “… we present the first in vivo evidence demonstrating the efficacy of intranasal monoclonal antibody (mAb) therapy targeting Artemisia pollen—a major global aeroallergen—in reducing features of allergic rhinitis and asthma.”
The prevalence of hay fever has been surging for decades and this is likely to continue. The change is so fast that genetic and health changes are unlikely to be solely responsible. Improved hygiene, the widespread use of antibiotics and antiseptics, lifestyle changes, diet, pollution, and the climate crisis are also thought to play a major role in this increase.
Allergen-specific immunotherapy (AIT) is an effective treatment strategy for allergic rhinitis caused by aeroallergens such as plant pollen, animal dander, or house dust, the authors explained. This approach may be used when conventional antihistamines can’t control symptoms.
AIT involves the repeated administration of gradually increasing doses of the allergen, followed by maintenance therapy over several years. “The primary goal is to induce immunological tolerance and reduce hypersensitivity by modulating the immune response, which in many cases leads to long-term symptom remission,” the team continued.
Over more recent decades, allergen-specific monoclonal antibody therapy has increasingly been investigated as a potential alternative. The team further noted, “Allergen-specific monoclonal antibodies (mAbs) have recently emerged as promising tools in allergy therapy, particularly for patients who do not respond adequately to allergen-specific immunotherapy …”
For allergen-specific monoclonal antibody therapy, researchers engineer antibodies of the IgG class, which either specifically recognize the allergen itself and block it, or bind to IgE antibodies and compete with allergen binding, the authors explained. In either case, the aim is to prevent the allergen from triggering an allergic reaction. “Although increased allergen-specific IgG levels do not consistently translate into clinical benefit,” the authors acknowledged, “a stronger association has been reported between clinical outcomes and the ability of IgG to block allergen-IgE binding.” A disadvantage of this approach is that typically, the antibodies need to be injected into the bloodstream.
For their newly reported study, the researchers injected mice with a dose of mugwort pollen, stimulating the animals to produce antibodies against it. White blood cells harvested from the animals’ spleens were then fused with laboratory-grown cancer cells from mice with multiple myeloma. This yielded five immortal “hybridoma” cell lines that each secreted a single type (monoclonal) of antibody against mugwort pollen. A suite of diagnostic tests showed that the most powerful was produced by the hybridoma cell line XA19, which was selected for further development.
To test antibody efficacy, purified antibodies from XA19 were administered to the interior of the nose of five mice that had been stimulated to become allergic to mugwort pollen through injections of pollen extract. Five additional mice that had been similarly sensitized, but received a placebo, served as positive controls. A further five mice were the negative controls, neither sensitized to the pollen nor given monoclonal antibodies.
After three weeks, all the mice were exposed three times under anesthesia to an aerosol of mugwort pollen, as well as to pollen extract delivered directly inside the nose.
The test results showed that pollen-sensitized mice given the XA19 antibody displayed a major reduction in allergy symptoms compared with control animals. The XA19 antibody-treated animals exhibited a weaker ear swelling response to the pollen (a common allergic reaction in rodents). They also rubbed their nose less frequently, indicating less irritation of the upper airways, and they showed less inflammation inside the nostrils. The full lung capacity of the treated animals was also preserved upon exposure to the pollen, and inside the lungs, levels of two inflammation-promoting cytokines were reduced.
“Intranasal mAb pretreatment led to a marked reduction in clinical symptoms of rhinitis, including a significant decrease in nasal rubbing episodes, and attenuated histopathological signs of inflammation in the nasal turbinates,” the team stated. “Pulmonary levels of Th2 cytokines (IL-4 and IL-5) were markedly reduced in mAb-pretreated mice, while total serum IgE levels remained largely unaffected.”
Tabynov further explained, “Our method acts immediately and locally at the lining of the nose, by neutralizing the allergen on contact … This ‘molecular shield’ not only prevents IgE antibodies from being activated, but may also reduce inflammation through other mechanisms, such as calming immune cell responses and promoting regulatory pathways.”
The researchers concluded that the monoclonal antibody from XA19 is effective in blocking allergic reactions against mugwort pollen triggered by IgE, at least in mice. “Our findings reveal, for the first time, that intranasal pretreatment with allergen-specific mAbs offers protective effects against Artemisia pollen, one of the most impactful airborne allergens worldwide,” they wrote. “Intranasal delivery of allergen-specific mAbs represents a novel, non-invasive strategy to prevent both upper and lower airway allergic inflammation … Our findings establish proof-of-concept for this approach and warrant further development.”
Tabynov continued, “Before this treatment can be tested in people, we need to adapt the antibody to make it suitable for humans—a process called ‘humanization’—and conduct additional preclinical safety and efficacy studies. If these are successful and provided we have adequate support, we could begin clinical trials in two to three years, though bringing it to market would likely take five to seven years. We are already planning for this transition and working on scaling up production.”
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