Prospects for a Vaccine in Allergic Diseases and Asthma

Abstract

Allergen-specific immunotherapy is widely used to treat allergic diseases, and current research is now focusing on the development of therapeutic vaccines acting on the IgE immune response following allergen challenge. The IgE immune response is dependent on genetic and environmental factors; production of IgE results from complex interactions among B cells, T cells, mast cells, basophils,surface and adhesion molecules and various cytokines. New vaccination methods under investigation involve allergen-specific or nonspecific methodology. Allergen-specific methods currently being developed include allergoids, passive saturation of effector cells, plasmid DNA immunisation and antigen-antibody complexes. The mechanisms of immunotherapy using allergen-specific methods differ with the allergens and the route of immunisation used (parenteral, intranasal, sublingual, oral or bronchial). Many vaccines being developed at present comprise synthetic, recombinant or highly purified subunit antigens, which although they have increased safety may also be less immunogenic.It is hoped that the addition of adjuvants will overcome this drawback. Methods of increasing the dose of allergen while reducing the possibility of an anaphylactic reaction include the use of non-anaphylactic isoforms of the allergens, alteration of the tertiary structure of the allergens and construction of minimal allergen-derived T cell peptides. Nonspecific approaches include humanised anti-IgE antibodies,moderation of the T(H)2 cytokine network and antisense oligodeoxynucleotide therapy.

Asthma and Mast Cell Biology

“…Activated mast cells appear to be the primary effector cell in the pathogenesis of atopic asthma. It has been previously reported that cellular infiltrate in bronchial biopsies and bronchoalveolar lavage of asthmatic patients contains several inflammatory cells, including mast cells (27), eosinophils, and T helper 2 (Th2) lymphocytes generating interleukin-3 (IL-3), IL-4, IL-5, IL-9, IL-13, and granulocyte macrophage colony-stimulating factor (GM-CSF) (28)(29).…”