WO2025185753A1 - Fusion protein inhalant for treating respiratory allergic diseases - Google Patents

Abstract

Disclosed in the present invention is a fusion protein inhalant for treating respiratory allergic diseases. The present invention provides a use of a fusion protein in preparation of a drug for treating respiratory allergic diseases. The fusion protein has an amino acid sequence as shown in SEQ ID NO: 3. The fusion protein inhalant provided by the present invention can effectively reduce inflammatory cell infiltration in lung tissue and around bronchi, and reduce airway hyperresponsiveness.

Description

Fusion protein inhaler for the treatment of respiratory allergic diseases

This application claims priority to PCT patent application number PCT/CN2024/080787, filed on March 8, 2024, entitled “Fusion protein inhaler for the treatment of respiratory allergic diseases”.

Technical Field

The present invention belongs to the fields of genetic engineering and immunology, and in particular relates to a fusion protein inhaler for treating respiratory allergic diseases.

Background Art

Allergic diseases are the sixth leading cause of acute and chronic illnesses and have a clear genetic predisposition. Common allergic diseases include allergic asthma, allergic rhinitis, hay fever, atopic dermatitis, allergic arthritis, urticaria, and anaphylactic shock.

Common respiratory allergic diseases include allergic rhinitis and allergic asthma. Allergic rhinitis mainly affects the patient's quality of life, while allergic asthma can be life-threatening in severe cases.

The mechanism of allergy development is as follows: when an allergen (antigen) first comes into contact with immune B cells, the B cells and T cells come into contact, differentiate into plasma cells, and produce large amounts of antibodies called IgE. These IgEs then bind to immune cells such as mast cells. Upon subsequent exposure to the allergen, the IgE-bound immune cells become activated, releasing substances like histamine, causing allergic symptoms and impacting the immune response. Current research on the pathogenesis suggests that allergens cross-link specific IgE antibodies with the IgE receptor FcεRI on the surface of allergic cells, thereby activating activation signaling pathways within the allergic cells and leading to the release of large numbers of intracellular granules. These granules contain numerous cytokines and chemokines, which act on surrounding tissues and organs, triggering an inflammatory response. This is often associated with clinical symptoms such as increased mucus secretion, nasal congestion, and bronchospasm.

Studies have shown that cross-linking the FcγRII receptor with the FcεRI receptor can induce inhibitory signals in mast cells or basophils, blocking the activation pathway within the cells, thereby inhibiting the release of active mediators and further suppressing allergic reactions. Therefore, using this reaction mechanism to develop a fusion protein that activates inhibitory signals in allergic reactions should be a new approach to treating allergies.

Summary of the Invention

The present invention provides a fusion protein inhaler and its application in treating respiratory allergic diseases. The fusion protein inhaler of the present invention can block the degranulation of allergic reaction cells and can effectively treat respiratory allergic asthma.

A first aspect of the present invention provides a drug for treating respiratory allergic diseases, the drug comprising a fusion protein having an amino acid sequence as shown in SEQ ID NO: 3; and a medically acceptable excipient;

The medically acceptable excipients include anti-adhesive agents, penetration enhancers, buffers, plasticizers, surfactants, defoamers, thickeners, inclusion agents, absorbents, humectants, solvents, propellants, solubilizers, cosolvents, emulsifiers, colorants, pH regulators, adhesives, disintegrants, fillers, lubricants, wetting agents, integrators, osmotic pressure regulators, stabilizers, glidants, flavoring agents, preservatives, foaming agents, suspending agents, coating materials, fragrances, diluents, flocculants and deflocculants, filter aids, release retardants or combinations thereof;

The respiratory allergic disease is selected from allergic rhinitis or allergic asthma.

In some specific embodiments, the fusion protein has a nucleotide sequence as shown in SEQ ID NO:4.

In some embodiments, the drug is a drug that reduces inflammatory cell infiltration and alleviates lung tissue fibrosis.

In some embodiments, the inflammatory cells are peribronchial inflammatory cells or lung tissue inflammatory cells.

In some embodiments, the drug is a drug that reduces airway hyperresponsiveness.

In some embodiments, the drug is a drug that reduces eosinophil infiltration of peribronchial or lung tissue.

In some embodiments, the drug is a drug that reduces neutrophil infiltration in peribronchial or lung tissue.

In some embodiments, the drug is a drug that reduces lymphocyte infiltration in peribronchial or lung tissue.

In some embodiments, the drug is a drug that reduces mononuclear cell infiltration of peribronchial or lung tissue.

In some embodiments, the medicament is a spray or inhaler.

The second aspect of the present invention provides the use of a fusion protein in the preparation of a drug for treating or preventing respiratory allergic diseases, wherein the fusion protein has an amino acid sequence as shown in SEQ ID NO: 3.

In some embodiments, the fusion protein has a nucleotide sequence as shown in SEQ ID NO:4.

In some embodiments, the respiratory allergic disease is selected from allergic rhinitis or allergic asthma.

In some embodiments, the drug is a drug that reduces inflammatory cell infiltration and alleviates lung tissue fibrosis.

In some embodiments, the inflammatory cells are peribronchial inflammatory cells or lung tissue inflammatory cells.

In some embodiments, the drug is a drug that reduces airway hyperresponsiveness.

In some embodiments, the drug is a drug that reduces eosinophil infiltration of peribronchial or lung tissue.

In some embodiments, the drug is a drug that reduces neutrophil infiltration in peribronchial or lung tissue.

In some embodiments, the drug is a drug that reduces lymphocyte infiltration in peribronchial or lung tissue.

In some embodiments, the drug is a drug that reduces mononuclear cell infiltration of peribronchial or lung tissue.

In some embodiments, the medicament is a spray or inhaler.

The third aspect of the present invention provides a fusion protein for treating or preventing respiratory allergic diseases, wherein the fusion protein has an amino acid sequence as shown in SEQ ID NO:3.

In some embodiments, the respiratory allergic disease is selected from allergic rhinitis or allergic asthma.

In some specific embodiments, the fusion protein has a nucleotide sequence as shown in SEQ ID NO:4.

The fourth aspect of the present invention provides a method for treating or preventing respiratory allergic diseases, administering the drug as described in the first aspect of the present invention or the fusion protein consisting of the amino acid sequence shown in SEQ ID NO: 3 to a subject in need.

In some embodiments, the respiratory allergic disease is selected from allergic rhinitis or allergic asthma.

In some specific embodiments, the fusion protein has a nucleotide sequence as shown in SEQ ID NO:4.

In some embodiments, the administration is respiratory administration.

In some embodiments, the level of inflammatory cells in the lung as assessed by total cell counts in bronchoalveolar lavage fluid, bronchial biopsy is reduced relative to pre-administration levels.

On the basis of conforming to the common sense in this field, the above-mentioned preferred conditions can be arbitrarily combined to obtain the preferred embodiments of the present invention.

The reagents and raw materials used in the present invention are commercially available.

The positive progress effect of the present invention is:

Fusion protein technology is used to specifically crosslink FcγRII and FcεRI on the surface of allergic cells, effectively activating inhibitory signaling pathways within the cells, thereby blocking the release of intracellular granules. Further studies in animal disease models have shown that fusion protein inhalers can block degranulation of allergic cells, reduce inflammatory cell infiltration, alleviate lung fibrosis, and reduce airway hyperresponsiveness. Fusion protein inhalers can reduce the infiltration of eosinophils, neutrophils, lymphocytes, and monocytes in peribronchial or lung tissue, and are effective in treating allergic rhinitis, allergic cough, allergic asthma, or anaphylactic shock.

BRIEF DESCRIPTION OF THE DRAWINGS

Figure 1A shows that mGE2 protein inhibits the degranulation reaction induced by DNP-IgE in wild-type mice; L is injected with mDNP-IgE on the left side, and R is injected with mDNP-IgE+mGE2 on the right side.

Figure 1B shows that mGE2 protein inhibits the degranulation reaction induced by DNP-IgE in FcγRII-deficient mice; L: mDNP-IgE was injected on the left side, and R: mDNP-IgE+mGE2 was injected on the right side.

FIG2 is a schematic diagram of the establishment of an OVA-induced asthma model in mice.

FIG3A is a diagram showing cell counts of bronchoalveolar lavage fluid (BAL).

FIG3B is a statistical graph showing the number of eosinophils, neutrophils, lymphocytes, and monocytes.

FIG3C is a statistical diagram of the number of macrophages.

Figure 4 is a stained image of bronchial pathological tissue sections.

FIG5 is a dose-response curve diagram showing the maximum drug resistance value after drug administration.

DETAILED DESCRIPTION

The term "FcγRIIb" is used to refer to the FcγRIIb receptor of any species present in nature, including any mammalian species. In some embodiments, the mammal is a human. FcγRIIb is an isotype of the low-affinity IgG receptor FcγRII that contains an immunoreceptor tyrosine-based inhibitory motif (ITIM). The FcγRIIb receptor is found on, for example, basophils, mast cells, B cells, and dendritic cells. FcγRIIb has three alternative splicing forms, designated FcγRIIb1, FcγRIIb1', and FcγRIIb2, which differ only in the sequence of the cytoplasmic domain. All three alternative splicing isoforms contain two extracellular immunoglobulin-like loops and a conserved ITIM motif located in the cytoplasmic tail and are explicitly included in the definition of FcγRIIb, along with other splicing variants that may be identified in the future.

The term "FcεRI" refers to the FcεRI receptor of any species, including any mammalian species found in nature. FcεRI is a member of the multiunit immune response receptor (MIRR) family of cell surface receptors. Receptors in the MIRR family of cell surface receptors are generally capable of transducing intracellular signals by binding to cytoplasmic tyrosine kinases.

Fusion proteins can be prepared, for example, by recombinant DNA technology or by chemical bonding to form a covalent bond or other well-known techniques in the art for forming fusion proteins. Providing an appropriate DNA sequence encoding the desired fusion protein allows the generation of the fusion protein using recombinant techniques well-known in the art. The coding sequence can be obtained from natural resources or synthesized or constructed using widely available starting materials by conventional methods. When the coding DNA is prepared synthetically, the codon preference of the intended host in which the DNA is to be expressed can be utilized.

Fusion proteins can be formed by combining the Fcε fragment with the Fcγ fragment via various linkers well known in the art.

To produce the fusion proteins of the present invention, one of ordinary skill in the art can use known techniques to synthesize or obtain a DNA molecule encoding an Fcε fragment or a portion thereof from readily available human DNA (combined with a DNA molecule encoding an Fcγ fragment or a portion thereof), and then insert the DNA molecule into a commercially available expression vector for use in known expression systems. Such systems include those in which the relevant fusion protein is produced as a single chain.

Those skilled in the art can use these commercially available expression vectors and systems or produce vectors using known methods and readily available starting materials. Expression systems containing the necessary control sequences (e.g., promoters and polyadenylation signals and preferably enhancers) are readily available for a variety of hosts and are well known to those skilled in the art. Thus, the desired protein can be produced in both prokaryotic and eukaryotic systems, thereby allowing the generation of a variety of processed forms of the protein.

Transfection/transduction refers to methods for introducing a gene into a cell and expressing the gene in the cell, which are known in the art. In the case of an expression vector, the vector can be easily introduced into a host cell, such as a mammalian cell, a bacterial cell, a yeast cell, or an insect cell, by any method in the art. For example, the expression vector can be transferred into the host cell by physical, chemical, or biological means.

IgE plays a key role in many acute and chronic allergic reactions, including, for example, asthma, allergic rhinitis, atopic dermatitis, severe food allergies, chronic urticaria and angioedema, and the serious physiological conditions of anaphylactic shock caused by, for example, food allergies, bee stings or penicillin allergies. The Fc portion of human IgE can bind to FcεRI or FcεRII cell surface receptors on various cell types such as basophils, mast cells, dendritic cells and B lymphocytes (B cells). When antigen binds to IgE, IgE binds to certain cell surface receptors on, for example, basophils and mast cells, and IgE binds to these cells causing vasoactive and proinflammatory mediators, including histamine. The mediators released when antigen-bound IgE bind to certain cell surface receptors significantly cause asthma and acute and late allergic reactions.

The term "pharmaceutically acceptable diluent, excipient, carrier or adjuvant" refers to a diluent, excipient, carrier or adjuvant that is physiologically acceptable to a subject while retaining the therapeutic properties of the pharmaceutical composition with which it is administered, such as a preservative, antioxidant, buffer, acidifier, alkalizer, solubilizer, complexation-enhancing agent, diluent, electrolyte, dextrose, stabilizer, bulking agent, defoaming agent, emulsifier, flavoring agent, sweetener, taste-masking agent, osmotic pressure regulator, surface tension regulator, viscosity regulator, density regulator or a combination thereof.

The term "subject" or "individual" may include, but is not limited to, mammals, such as humans or non-human mammals, e.g., domesticated animals, agricultural animals, or wild animals, as well as birds and aquatic animals. A "patient" is a subject who suffers from a disease, disorder, or condition, or is at risk of developing the disease, disorder, or condition, or who is otherwise in need of the compositions and methods provided herein. In some embodiments, the subject suffers from an autoimmune disease as described herein.

The term "treatment" refers to any sign of successful treatment or improvement of a disease or disorder. Treatment may include, for example, alleviating, delaying, or relieving the severity of one or more symptoms of a disease or disorder, or it may include reducing the frequency with which a patient experiences symptoms of a disease, defect, condition, or adverse condition. As used herein, "treating or preventing" is sometimes used herein to refer to a method that results in some degree of treatment or improvement of a disease or disorder, and contemplates a range of outcomes for that purpose, including, but not limited to, complete prevention of the disorder.

The term "prevent" refers to the prevention of a disease or condition, such as a tumor, in a patient. For example, if an individual at risk for developing an autoimmune disease is treated with the methods of the present disclosure, and the individual does not subsequently develop the autoimmune disease, the disease has been prevented in the individual for at least a period of time.

Airway hyperreactivity (AHR) refers to an excessively strong or premature airway constriction in response to various stimuli. If such stimuli, which are unresponsive or mild in normal individuals, cause significant bronchoconstriction in some individuals, this is considered AHR.

Reduction of Airway Hyperresponsiveness Bronchial hyperresponsiveness (also known as BH, bronchial hyperresponsiveness, AHR, or airway hypersensitivity) is a condition that predisposes to triggering or inducing bronchospasm. The methods disclosed herein, i.e., administering the formulations disclosed herein by inhalation, reduce BH by relaxing the ASM and reducing the sensitivity of the ASM. In some embodiments, the disclosure provides methods for reducing airway hyperresponsiveness by administering an effective amount of the formulations disclosed herein by inhalation.

Intrathecal injection (IT) aims to inject the drug into the subarachnoid space so that it can be delivered and diffused in the cerebrospinal fluid (CSF).

Methacholine (MCh) is the most commonly used stimulant in bronchial provocation tests.

Example 1: Construction and expression of mouse IgE and IgG Fc fusion protein (mGE2)

The FP4 gene was synthesized according to the nucleotide sequence shown in SEQ ID NO:3, and the synthesized FP4 (its amino acid sequence is shown in SEQ ID NO:3, and its nucleotide sequence is shown in SEQ ID NO:4) gene was cloned into the p-CI expression vector using SOE PCR and enzyme cutting methods. After verification by sequencing, the expression plasmid was transfected into CHO-S cells. After a large number of cells were cultured in 50% CD CHO + 50% Dynamis medium, the supernatant was collected, and the FP4 protein was isolated and purified from the culture supernatant of the transiently transfected cells using Protein A affinity chromatography.

The mGE2 gene was synthesized based on the mouse immunoglobulin IgE Fcε and IgG Fcγ sequences. The synthesized mouse mGE2 (FcεCH2-CH3-CH4-FcγHinge-CH2-CH3) (its amino acid sequence is shown in SEQ ID NQ:1, and its nucleotide sequence is shown in SEQ ID NO:2) gene was cloned into the p-CI expression vector using SOE PCR and enzyme cutting methods. After verification by sequencing, the expression plasmid was transfected into CHO-S cells. After culturing the cells in 50% CD CHO + 50% Dynamis medium, the supernatant was collected and mGE2 was isolated and purified from the culture supernatant of transiently transfected cells using Protein A affinity chromatography.

The amino acid sequence of the mGE2 fusion protein is shown in SEQ ID NO: 1:

Nucleotide sequence of mGE2:

Amino acid sequence of FP4 (SEQ ID NO: 3):

The underline represents the B region Fc-γ.

Nucleotide sequence encoding FP4 gene (SEQ ID NO: 4):

Example 2: mGE2 blocks allergic cell degranulation (PCA)

BALB/c mice were subcutaneously injected into the ears with 10 μg of mouse DNP-IgE (Sigma). The left ear contained DNP-IgE antibody alone, while the right ear contained DNP-IgE antibody plus 10 μg of mGE2. Two hours later, the allergen, 100 μg of DNP-human serum albumin (DNP-HAS) and 200 μL of 1% Evans blue (EVANS), was injected subcutaneously into the tail vein. Thirty minutes later, the ear skin color was observed. Results showed that mGE2 significantly inhibited allergic cell degranulation (Figure 1A).

Example 3: Inhibitory Effects of mGE2 in FcγRII-Deficient Mice

FcγRIIb was knocked out in C57BL/6 mice, creating FcγRIIb-deficient mice. The same procedures as in Example 2 were followed, revealing that the inhibitory effect of mGE2 on allergic cell degranulation was significantly abolished in FcγRIIb-deficient mice ( Figure 1B ). This suggests that the inhibitory effect of mGE2 on allergic cell degranulation occurs through cross-linking of FcεRI with FcγRIIb.

Example 4: Establishment of OVA-induced asthma model in mice

A standard ovalbumin (OVA) mixed with aluminum hydroxide adjuvant (Thermo) sensitization/challenge method was used to establish a mouse asthma model (see Figure 2).

Preparation of sensitizer: Weigh 0.018 g of ovalbumin and dissolve it in 6 mL of phosphate buffered saline to prepare an ovalbumin solution with a concentration of 3 mg/mL; take 70 μL of the 3 mg/mL ovalbumin solution and add it to 2.03 mL of phosphate buffered saline to prepare 2.1 mL of 0.1 mg/mL ovalbumin solution, then add an equal amount (2.1 mL) of aluminum hydroxide adjuvant to prepare a 0.05 mg/mL sensitizer, which is prepared for immediate use.

Preparation of the stimulant: Weigh 0.204 mg of ovalbumin and dissolve it in 4.08 mL of normal saline to prepare a 5% ovalbumin solution, which is ready for use.

Eighteen Balb/C mice weighing approximately 20 g were selected. Six mice were used as negative controls and injected intraperitoneally (i.p.) with saline/aluminum adjuvant at a volume of 200 μL. The other 12 mice were used as the asthma model group and were sensitized with ovalbumin VI/aluminum adjuvant via intraperitoneal injection. The mice were sensitized twice, on day 0 and day 7, respectively, with an injection volume of 200 μL.

On the 15th day and the 17th day, the rats were challenged twice with physiological saline (negative control group) and ovalbumin VI (asthma model group) by subarachnoid injection, with an injection volume of 50 μL.

On the 19th day, intravenous treatment was performed, and normal saline was used as a control. The asthma model mice were divided into two groups: an mGE2 treatment group and a positive control group with 6 mice in each group. Subcutaneous injection was used. The injection dose of the mGE2 treatment group was 10 mg/kg, and the positive control group used an equal volume of normal saline.

On the 20th day, the rats were challenged again with normal saline (negative and positive control groups) and ovalbumin VI (treatment group) injected into the subarachnoid space with an injection volume of 50 μL.

The therapeutic effect was evaluated on day 21, bronchoalveolar lavage (BAL) of mice was collected for cell counting and classification, and lung tissue was obtained for section staining and analysis.

Example 5: Role of mGE2 in OVA-induced allergic asthma

The clinical manifestations of allergic asthma are primarily inflammatory infiltrates and increased airway reactivity within the lung tissue. In bronchoalveolar lavage (BAL) fluid (BAL), the total number of cells in the mGE2-treated group was significantly lower than in the control group (Figure 3A). Further cell classification revealed a significant decrease in the number of eosinophils, neutrophils, lymphocytes, and monocytes (Figure 3B). These results suggest that mGE2 can mitigate inflammatory cell infiltration during asthma, thereby alleviating the inflammation of allergic asthma. Bronchial pathological tissue staining also revealed significantly less inflammatory cell infiltration around the bronchi in the treated group than in the control group (Figure 4). Invasive assessment of respiratory mechanics was performed using an intact, intubated, anesthetized mouse model similar to that previously reported. Briefly, mice were anesthetized with approximately 60 mg/kg of pentobarbital, and the trachea was then intubated with an 18-gauge metal needle. A computer-controlled rodent ventilator (flexiVent) was then used to deliver a tidal volume of 10 mL/kg (approximately 250 μL/breath) at a rate of 150 breaths per minute, with a positive end-expiratory pressure of 2.5 cm _H₂O . Dynamic pulmonary resistance was measured by fitting a linear, first-order, single-compartment model of airway mechanics to measurements of airway pressure, volume, and airflow during a single sinusoidal perturbation with an amplitude of 150 μL at 2.5 Hz for approximately 1.2 seconds, using the manufacturer's software (flexiVent). The mean of two tolerance measurements performed before methacholine administration was then established as a baseline. Subsequently, increasing concentrations of methacholine (1.25, 3.125, 12.5, and 50 mg/mL) were delivered to the airways via the ultrasonic nebulizer reservoir, which temporarily diverted the inspiratory limb of the ventilator for 30 seconds. Drug tolerance was measured at 30-second intervals for 5 minutes after each administration, and a dose-response curve was constructed using the maximum drug tolerance value after each administration. The results showed that after administration of 50 mg/mL methacholine, mGE2 decreased airway hyperresponsiveness by 64% compared to the control group, indicating that mGE2 effectively reduced airway hyperresponsiveness (Figure 5).

Although the above describes specific embodiments of the present invention, it should be understood by those skilled in the art that these are merely illustrative and that various changes or modifications may be made to these embodiments without departing from the principles and essence of the present invention. Therefore, the scope of protection of the present invention is defined by the appended claims.

Claims (15)

A drug for treating respiratory allergic diseases, characterized in that the drug comprises a fusion protein having an amino acid sequence as shown in SEQ ID NO: 3; and a medically acceptable excipient; The medically acceptable excipients include anti-adhesive agents, penetration enhancers, buffers, plasticizers, surfactants, defoamers, thickeners, inclusion agents, absorbents, humectants, solvents, propellants, solubilizers, cosolvents, emulsifiers, colorants, pH regulators, adhesives, disintegrants, fillers, lubricants, wetting agents, integrators, osmotic pressure regulators, stabilizers, glidants, flavoring agents, preservatives, foaming agents, suspending agents, coating materials, fragrances, diluents, flocculants and deflocculants, filter aids, release retardants or combinations thereof; The respiratory allergic disease is selected from allergic rhinitis or allergic asthma; Preferably, the fusion protein has a nucleotide sequence as shown in SEQ ID NO:4. The drug according to claim 1, characterized in that the drug is a drug that reduces inflammatory cell infiltration and alleviates lung tissue fibrosis; Preferably, the inflammatory cells are inflammatory cells around the bronchus or inflammatory cells in lung tissue. The drug according to claim 1 or 2, characterized in that the drug is a drug that reduces airway hyperresponsiveness. The drug according to any one of claims 1 to 3, characterized in that the drug is a drug for reducing eosinophil infiltration around bronchial or lung tissue; and/or, the drug is a drug that reduces neutrophil infiltration around bronchial or lung tissue; and/or, the drug is a drug that reduces lymphocyte infiltration in peribronchial or lung tissue; And/or, the drug is a drug that reduces mononuclear cell infiltration around bronchial tissue or lung tissue. The drug according to any one of claims 1 to 4, wherein the drug is a spray or an inhalant. Use of a fusion protein in the preparation of a drug for treating or preventing respiratory allergic diseases, wherein the fusion protein has the amino acid sequence shown in SEQ ID NO: 3; Preferably, the respiratory allergic disease is selected from allergic rhinitis or allergic asthma; and/or, The fusion protein has a nucleotide sequence as shown in SEQ ID NO:4. The use according to claim 6, wherein the drug is a drug for reducing inflammatory cell infiltration and alleviating lung tissue fibrosis; Preferably, the inflammatory cells are inflammatory cells around the bronchus or inflammatory cells in lung tissue. The use according to claim 6 or 7, characterized in that the drug is a drug that reduces airway hyperresponsiveness. The use according to any one of claims 6 to 8, characterized in that the drug is a drug for reducing eosinophil infiltration around bronchial or lung tissue; and/or, the drug is a drug that reduces neutrophil infiltration around bronchial or lung tissue; and/or, the drug is a drug that reduces lymphocyte infiltration in peribronchial or lung tissue; And/or, the drug is a drug that reduces mononuclear cell infiltration around bronchial tissue or lung tissue. The use according to any one of claims 6 to 9, wherein the drug is a spray or an inhalant. A fusion protein for treating or preventing respiratory allergic diseases, characterized in that the fusion protein has the amino acid sequence shown in SEQ ID NO: 3; Preferably, the respiratory allergic disease is selected from allergic rhinitis or allergic asthma. The fusion protein as described in claim 11 is characterized in that the fusion protein has a nucleotide sequence as shown in SEQ ID NO:4. A method for treating or preventing respiratory allergic diseases, characterized by administering the drug according to claim 1 or the fusion protein having the amino acid sequence shown in SEQ ID NO: 3 to a subject in need thereof; Preferably, the respiratory allergic disease is selected from allergic rhinitis or allergic asthma; and/or, The fusion protein has a nucleotide sequence as shown in SEQ ID NO:4. The method of claim 13, wherein the administration is respiratory administration. The method of claim 13 or 14, wherein the level of inflammatory cells in the lung as assessed by total cell count in bronchoalveolar lavage fluid or bronchial biopsy is reduced relative to pre-administration levels.