Chemical modification of birch allergen extract leads to a reduction in allergenicity as well as immunogenicity.
BACKGROUND
In Europe, specific immunotherapy is currently conducted with vaccines containing allergen preparations based on intact extracts. In addition to this, chemically modified allergen extracts (allergoids) are used for specific allergy treatment. Reduced allergenicity and thereby reduced risk of side effects in combination with retained ability to activate T cells and induce protective allergen-specific antibody responses has been claimed for allergoids. In the current study, we compared intact allergen extracts and allergoids with respect to allergenicity and immunogenicity.


METHODS
The immunological response to birch allergen extract, alum-adsorbed extract, birch allergoid and alum-adsorbed allergoid was investigated in vitro in human basophil histamine release assay and by stimulation of human allergen-specific T cell lines. In vivo, Bet v 1-specific IgG titers in mice were determined after repetitive immunizations.


RESULTS
In all patients tested (n = 8), allergoid stimulations led to reduced histamine release compared to the intact allergen extract. However, the allergoid preparations were not recognized by Bet v 1-specific T cell lines (n = 7), which responded strongly to the intact allergen extract. Mouse immunizations showed a clearly reduced IgG induction by allergoids and a strongly potentiating effect of the alum adjuvant. Optimal IgG titers were obtained after 3 immunizations with intact allergen extracts, while 5 immunizations were needed to obtain maximal response to the allergoid.


CONCLUSIONS
The reduced histamine release observed for allergoid preparations may be at the expense of immunological efficacy because the chemical modifications lead to a clear reduction in T cell activation and the ability to induce allergen-specific IgG antibody responses.
Würtzen
Peter Adler
PA
ALK-Abelló A/S, Vaccine Research and Experimental Immunology, Hørsholm, Denmark. PAW@DK.ALK-Abello.com
Lund
Lise
L
Lund
Gitte
G
Holm
Jens
J
Millner
Anders
A
Henmar
Helene
H
D000327:Adsorption; D000485:Allergens / Q000737:chemistry / Q000276:immunology / Q000494:pharmacology*; D000080384:Allergoids; D000534:Alum Compounds / Q000737:chemistry; D000818:Animals; D052179:Antigens, Plant / Q000737:chemistry / Q000276:immunology / Q000494:pharmacology*; D029662:Betula / Q000276:immunology*; D002460:Cell Line; D005976:Glutaral / Q000737:chemistry; D006632:Histamine / Q000378:metabolism; D006801:Humans; D006967:Hypersensitivity; D007114:Immunization; D007074:Immunoglobulin G / Q000097:blood / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D010936:Plant Extracts / Q000737:chemistry / Q000276:immunology / Q000494:pharmacology*; D010940:Plant Proteins / Q000737:chemistry / Q000276:immunology / Q000494:pharmacology*; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology
D000485:Allergens; D000080384:Allergoids; D000534:Alum Compounds; D052179:Antigens, Plant; D007074:Immunoglobulin G; D010936:Plant Extracts; D010940:Plant Proteins; C041524:aluminum sulfate; D006632:Histamine; D005976:Glutaral