Prevention of allergy in children

Abstract

The present invention relates to a use of bacterial superantigens in the manufacture of a pharmaceutical composition for mucous membrane administration for the prevention of inflammatory disorders in newborn infants, such pharmaceutical compositions, as well as method for prevention of inflammatory disorders.

Description

TECHNICAL FIELD [0001] The invention refers to the use of a bacterial superantigen for administration onto the mucous membrane in newborn infants for the prevention of allergies, autoimmune and inflammatory disorders. BACKGROUND OF THE INVENTION [0002] A number of diseases are characterized by an exaggerated or untoward immune reactivity against harmless antigens. Such diseases include allergies, autoimmune diseases and inflammatory bowel diseases. Normally, immune responses to harmless antigens are suppressed, a mechanism called tolerance. Tolerance to specific antigens, either exogenous or endogenous, may be induced either by mucosal or systemic exposure. Tolerance occurs because helper T-cells are deleted, paralyzed or suppressed by other T-cells, so called regulatory T-cells. Allergies [0003] Allergies are defined as enhanced immune reactivity to one or several harmless environmental antigens, so called allergens. In IgE-mediated allergies, the allergic individual mounts an IgE...

AI Technical Summary

Benefits of technology

[0027] A puzzling observation was that only very early colonization by toxin-producing S. aureus gave a significant protective effect. Although infants who did not develop allergy were persistently more often colonized by toxin-producing S. aureus than those who developed allergy, colonization which was initiated after the first week seemed to have little effect. This probably relates to either of two factors. Either the toxin is only produced in the intestines in very early life. Since S. aureus has only recently been recognized as an intestinal colonizer, it is not known whether the necessary conditions for toxin production are at hand in the infantile intestinal tract. Perhaps production of toxins requires the presence of oxygen. The intestinal milieu is quite rich in oxygen during the first days of life, but becomes more and more anaerobic once more different types of bacteria establish in the intestinal tract. Secondly, S. aureus decrease quite rapidly in population numbers after the first period of life, probably reflecting that they are not “professional” intestinal bacteria but can only reach substantial population numbers in the absence of a more complex intestinal flora. After some months S. aureus has decreased substantially and the amount of toxin produced may not be large enough to affect the immune system. A third factor may be that the intestinal mucosa is more permeable to S. aureus toxins in very early life. A fourth factor may be that once breast-feeding has been established, the antibodies in the mother's milk against S. aureus toxins reduce its chances to affect the intant's mucosa. Due to these factors a very early (within 7 days) colonization of S. aureus toxin-producing strains is probably essential. However, a direct administration of the bacterial superantigen onto the mucous membrane in appropriate doses may extend the time span for establishing the preventive effect up to the age of three months.

Problems solved by technology

However, these measures have been completely ineffective, in that only minute amounts of antigen is needed to trigger IgE production.

However, it is not known which types of microbes are important for this to occur.

There is an endless variety of bacteria, viruses and parasites, some of which might be important in providing the right type of stimuli to the immune system, others which may be ineffective, or even increase the risk of developing hypersensitivity or inflammation.

This means that they bind to and activate a large proportion (10-30%) of the T-cells in human beings or animals, resulting in a massive cytokine production that may lead to shock and severe symptoms, even death.

It has, thus, been suggested that toxins elaborated by S. aureus can worsen the reaction by stimulating T-cells, leading to tissue damage.

However a treatment that results in anergy or deletion of T-cells would not be recommended as prevention for allergy in children since decreased T-cell function would lead to a poor defense against infections.

It has been described that the number and function of CD25+ Treg can be increased by in vitro stimulation with polyclonal activators as well as specific antigens and transfer of these antigen-expanded cells into mice results in delayed development of autoimmune disease in susceptible mice.

This observed activation / reduction together with the fact that superantigen in the blood circulation leads to shock in humans are the main reasons why Staphyloccocal enterotoxins administered into the blood are unsuitable for treatment of humans.

However, it is completely unethical and impossible to do such procedures as preventive measures in small children.

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