Background
Inspiration
Our Solution
Reference
Allergy is a global health concern, affecting millions of people worldwide. The prevalence of allergic diseases, such as allergic rhinitis, asthma, food allergies, and atopic dermatitis, has been steadily rising, with significant impacts on individuals’ quality of life, healthcare systems, and economies. It threatens all humans regardless of age, gender or anything. According to WAO White Book on Allergy WAO-WhiteBook-2013.pdf, 300 million people have asthma, 50-80% have allergic asthma. 220-520 million people are allergic to food, 400 billion people have allergic rhinitis. 10% of the world’s population is allergic to drug. Approximately 30-40% of the global population suffers from allergies.
Allergic diseases represent a significant and growing public health burden worldwide, with their prevalence and specific allergen profiles exhibiting marked geographical variations due to differences in climate, vegetation, dietary habits, and environmental exposures. Guangdong Province, a major coastal region in southern China with a subtropical climate, presents a distinctive allergic disease landscape characterized by high sensitization rates to specific aeroallergens and food allergens (Zeng et al., 2017). In Guangdong Province, common allergens are as follows:
House dust mite: Due to the warm and humid climate in Guangdong, which is very conducive to the growth of dust mites, data shows that the positive rate of dust mite sIgE in adults in the Guangzhou area can reach 34.41%, and the allergic situation in children is even more prominent. (Wang, 2012).
Seafood: Shrimp and crab are the most common allergenic seafood; the detection rate of shrimp allergies among children is relatively high. Allergic symptoms can involve the skin (itching, rash), digestive tract (nausea, vomiting), and respiratory tract (itchy nose, swelling of the throat), and in severe cases, they may even endanger life (Leung, Jie, Gu, & Wong, 2025).
Pollen: Patients in this area often suffer from allergies to both tree pollen and grass pollen, which is closely related to the subtropical climate of the region, where woody plants are abundant and the pollen season is long, as well as the widespread distribution of herbaceous plants (Luo et al., 2016).
Figure 1 Sensitization to individual allergens in Guangdong(Zeng et al., 2017) d1: house dust mite; i6: cockroach; tx4: tree pollen mix; f23: crab; f24: shrimp; f2: milk.
Allergies represent a significant and often underestimated threat to human health, capable of escalating from disruptive discomfort to life-threatening emergencies in moments. Far beyond simple annoyances, allergic reactions occur when the body’s immune system mistakenly launches a violent attack against harmless substances, treating them as dangerous invaders. This internal assault can cripple daily life with debilitating symptoms like relentless sneezing, agonizing itching, swollen eyes, and severe respiratory distress. At its most extreme, this misguided defense can trigger anaphylaxis—a catastrophic, whole-body reaction causing airways to swell shut, blood pressure to plummet dangerously, and vital organs to fail, leading to suffocation, cardiac arrest, and death without immediate treatment. These reactions disproportionately endanger the young, the elderly, and those with asthma, turning everyday environments into potential hazard zones. Allergies are not minor inconveniences; they are potentially lethal malfunctions of the immune system demanding vigilance and respect as serious medical conditions. Ignoring them can have fatal consequences.
So, why does an allergy trigger such a severe reaction?
Allergies are an overreaction of the immune system to allergens (typically harmless foreign substances) and can be divided into a sensitization phase and an effector phase. The sensitization phase occurs when the allergen first enters the body. The allergen stimulates B cells to produce a large number of allergen-specific IgE antibodies. These IgE antibodies then bind to the FcεRI receptors on the surface of mast cells, thereby completing the sensitization process. The effector phase occurs when the same allergen re-enters the body and binds to the IgE on mast cells, causing cross-linking of FcεRI receptors. This stimulates the mast cells to release inflammatory substances, triggering an allergic reaction.
Figure 2 Mechanism of allergic inflammation in type I hypersensitivity reactions(González-de-Olano & Álvarez-Twose, 2018)
Here are the sensitization mechanisms of common allergens:
Figure 3 The allergic mechanisms of pollen, house dust mites, and seafood(Gerlinger, 2024; Lee, 2016; Reithofer & Jahn-Schmid, 2017).
- Traditional allergy treatment
The traditional allergy treatment methods have significant limitations in clinical application, mainly manifested in two aspects: environmental control and drug therapy.
- Environmental control
Strategies (such as using anti-allergy bedding, avoiding going outside during pollen season, and strictly avoiding allergic foods) are theoretically effective, but in practice, it is often difficult to completely avoid ubiquitous allergens (such as airborne pollen and dust mites). Their effectiveness highly depends on the patient's self-discipline and environmental conditions, so they are usually only applicable to patients with mild symptoms.
- Drug treatment
Drug treatment, such as widely used antihistamines (like loratadine and cetirizine) and glucocorticoids, mainly works by antagonizing histamine receptors or inhibiting inflammatory responses, thereby quickly alleviating allergic symptoms. However, most of these drugs can only provide symptomatic treatment and cannot achieve a cure. Long-term use faces many problems: some patients may develop resistance, and even the symptoms are highly likely to recur after discontinuation of the medication. This is because drug treatment does not change the immunological mechanism underlying allergic diseases - that is, the "IgE-mediated Th2-type immune response" that the body has to harmless substances.
Therefore, developing specific treatments (such as allergen-specific immunotherapy) that can induce immune tolerance and fundamentally reverse the immune response has become the current focus and direction of research.
- Allergen Immunotherapy
Allergen-specific immunotherapy (AIT) is a treatment that slowly exposes patients to small, increasing amounts of an allergen to reduce allergic reactions over time. The therapy began in 1911 when Noon and Freeman first used pollen extracts to treat hay fever (Noon, 1953). Since then, AIT has improved significantly, with options like allergy shots (SCIT) and under-the-tongue drops or tablets (SLIT) making treatment safer and more convenient (Canonica & Compalati, 2009). Unlike allergy medications that only relieve symptoms temporarily, AIT can provide long-term relief by teaching the immune system to tolerate allergens better(Akdis & Akdis, 2014). Studies show it can reduce symptoms, decrease the need for medication, and even prevent allergies from worsening—such as stopping hay fever from turning into asthma, especially in children (Durham & Stocker, 2012). Recent advances, like purified allergen extracts and immune-boosting additives, have made AIT more effective and precise (Jutel, 2015). Today, it remains the only treatment that can change the course of allergic diseases, offering benefits that last for years after treatment ends.
Although the existing AIT therapy has potential in treating allergic diseases, it also has many limitations. Firstly, during the treatment process, severe allergic reactions may occur, so it needs to be carried out under the supervision of medical professionals. Additionally, AIT usually targets specific allergens, and treating patients with multiple allergies may make the treatment more complicated. The treatment period is long, usually taking several months to several years, which may pose certain challenges to the patient's patience. Moreover, there are significant individual differences, and some patients may have limited effects and may experience side effects at the injection site, which may affect the comfort of the treatment. Furthermore, the economic burden of AIT is heavy, including diagnosis and treatment costs as well as medication expenses. Finally, certain groups of people (such as pregnant women and patients with severe asthma) may not be suitable for this therapy.
What we want is a safer treatment, providing minimal side effects, while also being more effective in addressing the root causes of conditions. Additionally, we desire solutions that offer lasting benefits, helping patients maintain their health over the long term and reducing the likelihood of recurring issues. In short, we seek a balanced approach that ensures safety, efficacy, and sustainability in patient care.
Our project aims to address the core issues faced by AIT by integrating three strategies. The aim is to reduce side effects, enhance treatment efficacy, and significantly improve accessibility and patient compliance. These three strategies are:
(1) Rational design of hypoallergenic proteins
(2) Multi-allergen fusion constructs enabling broad-spectrum desensitization
(3) Microneedle-based delivery platform for painless, sustained, and user-friendly administration.
Figure 4 Diagram of our project strategy and the DBTL cycle.
- (1) Redesigning hypo-allergens:
Conventional AIT utilizes crude extracts of natural allergens, often containing high levels of IgE-binding epitopes. These can trigger severe allergic reactions, including anaphylaxis. To overcome this, we experimentally engineered recombinant hypoallergenic derivatives from six common allergens (Phl p1, Bet v1, Der p1, Der p2, Met e1, Cyp c1) (Ball et al., 2009; Hong, 2019; Reginald & Chew, 2018; Swoboda et al., 2007; Wai et al., 2014; Wallner et al., 2011). By removing or mutating conformational IgE epitopes while preserving T cell epitopes, these molecules retain immunogenicity for tolerance induction, but significantly reduce hypersensitivity risk. The designed antigens can induce IgG-blocking antibodies, competing with IgE.
- (2) Fusion Allergen:
Many allergic individuals are sensitized to multiple allergens. Traditional AIT requires multiple injections and separate formulations. To address this issue, we have fused and expressed hypoallergenic proteins from similar allergic phenomena, aiming to achieve broad-spectrum therapeutic effects. Additionally, we also incorporated the self-assembling peptide EFK8 into the fusion protein to form protein oligomers, thereby prolonging the half-life of the product and reducing the frequency of administration.
- (3) Microneedle-Based Delivery
We have also combined micro-needle technology with allergy immunotherapy, aiming to revolutionize the administration route of traditional therapies through a painless, efficient, and patient-friendly approach. This minimally invasive method significantly reduces patients' fear and discomfort, enhances the convenience of medication administration, and long-term treatment compliance. It is expected to provide an even more comfortable, safe, and effective long-term management strategy for allergy patients.
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