Methods of prevention and treatment of asthama, and allergic conditions

Abstract

The present invention relates to allergy vaccines and methods of treating and / or preventing asthma, and allergic conditions. The invention is based on the discovery that inhibiting the ligand / receptor interactions involving, e.g., IgE, IL-3, IL-4, IL-5, IL-6, IL-10, IL-13, interferon-alpha, histamine, leukotriene, and their respective receptors, inhibits production of IgE thereby treating or preventing such diseases or conditions. Competitive inhibition of such receptor / ligand interactions is accomplished by immunizing a human or veterinary patient with the interleukin, interferon-alpha, histamine, leukotriene, their receptors, in any combination. Also, the invention relates to inhibiting receptor / ligand interactions involved in IgE production by competitively inhibiting such interactions by administering antibodies to the ligands, receptors, or both, as well as by administering analogs of the receptors (e.g., soluble receptors not associated with a cell).

Description

BACKGROUND OF THE INVENTION [0001] The development of allergy or other types of immune hypersensitivity is an important undesirable effect of acquired immunity in mammals, particularly humans. There are several types of allergy. The present invention is concerned with atopic allergy. Atopic allergy is characterized by an excess production of IgE antibody, which attaches to mast cells and basophils. A single mast cell or basophil may bind as many as a half a million molecules of IgE. When an antigen binds to at least two IgE molecules bound on the surface of a mast cell or a basophil, the cell ruptures or otherwise is caused to release several substances including histamine, leukotrienes (previously referred to as “slow reacting substance of anaphylaxis”), eosinophilic chemotactic factor, proteases, neutrophil chemotactic substance, heparin, platelet activating factors and bradykinin. Release of these substances results in dilation of local blood vessels, attraction of eosinophils an...

AI Technical Summary

Benefits of technology

[0043] The invention includes a method of preventing an allergic response in a mammal. The method comprises administering to the mammal an allergy vaccine comprising at least one nucleic acid encoding an ingredient selected from the group consisting of an IgE, an IgE receptor, an interleukin involved in the production of IgE in a mammal, a receptor for an interleukin involved in the production of IgE in a mammal, an interferon-alpha, an interferon-alpha receptor, a histamine, a histamine receptor, a leukotriene, and a leukotriene receptor, thereby preventing an allergic response in a mammal.

[0100] The invention includes a pharmaceutical composition comprising at least one isolated nucleic acid encoding a protein selected from the group consisting of an IgE, an IgE receptor, an interleukin involved in production of IgE in a mammal, a receptor for an interleukin involved in production of IgE in a mammal, an interferon-alpha, an interferon-alpha receptor, a histamine, a histamine receptor, a leukotriene, a leukotriene receptor, in a pharmaceutically-acceptable carrier, in an amount effective for preventing an allergic response in a mammal.

Problems solved by technology

The development of allergy or other types of immune hypersensitivity is an important undesirable effect of acquired immunity in mammals, particularly humans.

Release of these substances results in dilation of local blood vessels, attraction of eosinophils and neutrophils to the reactive site, damage to local tissues by proteases, increased permeability of the capillaries and loss of fluid into the tissues, and contraction of smooth muscle cells.

Death may result from circulatory shock within minutes.

In addition, leukotrienes are released which may elicit a massive asthma attack and death by suffocation.

Both of these effects cause rapid fluid leakage into the tissues of the nose and the nasal linings become swollen and secretory.

Asthma is characterized by spastic contraction of the smooth muscle in the bronchioles, which causes extreme difficulty in breathing.

The drawbacks of such treatments is the necessity that they are used essentially subsequent to the allergic event and do not prevent future allergic events in the patient.

These compounds have several disadvantages in that there is a risk that they will not be effective and despite their administration, the asthma attack will continue.

In addition, several side effects are associated with prolonged use of these type of compounds, particularly in the case of corticosteroids and beta-adrenergic agents; further, there is a progressive loss of sensitivity to these treatments after prolonged use.

In severe asthma, these compounds are only of limited efficacy.

Further, these compounds are non-selective, i.e., they do not specifically target the lung, therefore, side-effects affecting other organs are a potential risk.

In addition, there is an increasing body of evidence which indicates there may be an increased risk of dying from bronchial asthma following prolonged treatment of asthma using long-acting beta-adrenergic agents such as fenoterol (Pearce et al., 1990, Thorax 45:170-175; Spitzer et al., 1992, New Engl. J. Med. 326:560-561).

To date, there are no long-term preventative treatments available for allergies in humans.