Specific
immunotherapy is based on the administration of increasing doses of
allergens to allergic patients with the aim of inducing a state of
antigen-specific unresponsiveness. Specific
immunotherapy is one of the few causative treatment approaches for Type I
allergy but may cause numerous side effects, including local inflammatory reactions, systemic manifestations (e.g.,
asthma attacks) and in the worst case,
anaphylactic shock which may lead to death. Several attempts have been made in the past to reduce the rate of side effects. They included the chemical modification of
allergen extracts to reduce their allergenic activity and the adsorption of
allergen extracts to adjuvants to prevent the systemic release of
allergens after administration. During the last decade, cDNAs coding for the most relevant
allergens have been isolated and the corresponding
allergens have been produced as recombinant molecules. Using
allergen-encoding cDNAs, the amino acid sequence of
allergens or purified recombinant
allergens several strategies can now be applied to produce
allergen derivatives with reduced allergenic activity for
allergy vaccination in a controlled and reproducible manner. Currently,
allergen-encoding cDNAs are used to engineer recombinant hypoallergenic
allergen derivatives. According to the amino acid sequences and experimental
epitope mapping data, synthetic
peptides representing T- or
B-cell epitopes are produced and purified recombinant
allergens are coupled to novel adjuvants for
vaccine formulation. In this article, strategies for the production and evaluation of
allergen derivatives with reduced allergenic activity for
allergy vaccination are described. These new
vaccines hold great promise to improve the current practice of
allergen-specific
immunotherapy and maybe also used for prophylactic vaccination in the future.