Genetically engineered vaccines.
The application of recombinant DNA technology to allergen research has provided the sequence information and genetic material to produce new types of allergy vaccines. One general strategy has been to use the knowledge to produce synthetic peptides that represent selected T-cell or B-cell epitopes. The production of genetically engineered allergens provides an alternative strategy to construct hypoallergenic vaccines, which can provide a better and less selected representation of the epitopes. Many strategies have been used to produce such hypoallergens, and their ability to reduce allergenicity has been amply demonstrated by skin and nasal provocation tests. The retention of T cell-stimulating activity has also been demonstrated, and a consistent feature of the vaccines has been, despite the reduced immunoglobulin E (IgE)-binding reactivity, the ability to induce anti-allergen IgG antibody. The lead hypoallergens have been polypeptide fragments and trimeric constructs of the birch allergen Bet v 1. A clinical trial with these medicaments has shown the ability to modify IgE and IgG antibody production, skin test reactivity, and symptom scores. This is the first trial of a recombinant allergy vaccine, and it has set a benchmark for further studies. A new generation of hypoallergens is now being produced based on the detailed knowledge of the tertiary structures of the allergens and of the T-cell and B-cell epitopes. The modifications have been made to change the topography of the allergens while retaining a stable, folding structure. In the case of Bet v 1, tertiary structures of hypoallergens have been determined. Structurally modeled hypoallergens have been produced for pollen, venom, food, and latex allergens, with promising characteristics from preclinical studies.
Thomas
Wayne R
WR
Centre for Child Health Research, University of Western Australia, Telethon Institute for Child Health Research, PO Box 855, West Perth 6872, 100 Roberts Road, Subiaco 6008, Western Australia. wayne@ichr.uwa.edu.au
Hales
Belinda J
BJ
Smith
Wendy-Anne
WA
D000485:Allergens / Q000235:genetics / Q000276:immunology / Q000627:therapeutic use; D000818:Animals; D006801:Humans; D006967:Hypersensitivity / Q000188:drug therapy; D015202:Protein Engineering; D014614:Vaccines, Synthetic / Q000276:immunology*
D000485:Allergens; D014614:Vaccines, Synthetic