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Original Article

 

Allergoid-specific T-cell reaction as a measure of the immunological response to specific immunotherapy (SIT) with a Th1-adjuvanted allergy vaccine

 

V. von Baehr1, A. Hermes2, R. von Baehr1, H.-P. Scherf2, H.-D. Volk3, K. J. Fischer von Weikersthal-Drachenberg4, and S. Woroniecki5

1 Laboratory Center Berlin, Department of Immunology. Landgrafenstraße 16, 10787 Berlin, Germany
2 Practice Sharing General and Internal Medicine, Frankfurter Allee 165, D-10365 Berlin, Germany
3 Institute of Medical Immunology, Charité Medical School – Campus Mitte, Humboldt-University Berlin,
D-10098 Berlin, Germany
4 Bencard Allergie GmbH, Munich, Germany
5 Allergy Therapeutics UK Ltd, Worthing, UK

J Invest Allergol Clin Immunol 2005; Vol. 15(4): 234-241

 

 Abstract


Background: Specific immunotherapy (SIT) is believed to modulate CD4+ T-helper cells. In order to improve safety, SIT vaccines are often formulated with allergoids (chemically modified allergens). Interaction between T-cells and allergoids is necessary to influence cellular cytokine expression. There have been few reports on identification the early cellular effects of SIT.

Method: Patients allergic to grass and/or mugwort pollen (n= 21) were treated with a 4-shot allergy vaccine (Pollinex Quattro) containing appropriate allergoids (grass/rye and/or mugwort) adsorbed to L-tyrosine plus a Th1 adjuvant, monophosphoryl lipid A (MPL®). Fourteen grass-allergic patients served as untreated controls. Using the peripheral blood mononuclear cells of these patients, an optimized lymphocyte transformation test (LTT) was employed to monitor the in vitro proliferative response of T-cells to an allergoid challenge (solubilised Pollinex Quattro) before the first and last injection and then 2 and 20 weeks after the final injection. Control challenges utilised preparations of a similar pollen vaccine without the adjuvant MPL® and a tree pollen vaccine with and without MPL®.

Results: The LTT showed increased LTT stimulation indices (SI) in 17/20 SIT patients when the solublised vaccine preparation was used as a challenge before the last injection and 2 weeks after, in comparison to pre-treatment levels. Twenty weeks after therapy, the SI decreased to baseline level. A vaccine challenge without MPL® gave
lower SI levels. A challenge of a clinically inappropriate tree allergoid vaccine gave no response, and a nontreated group also showed no response.

Conclusion: Following a short-course SIT adjuvated with MPL®, challenges of allergoids were shown to activate allergen-specific T cells in vitro. There was an additional stimulating effect when the challenge was in combination with MPL®. There were no non-specific effects of MPL®, shown by the tree allergoid/ MPL® control. The timing of the response was closely correlated to the treatment course; reactivity fell two weeks after the final injection and 20 weeks later it was at baseline level. Thus an immunological response to SIT was detected after very few injections. This methodology could provide a basis for monitoring the immediate progress of allergy vaccinations.

Key words: Lymphocyte transformation, T cells, SIT, allergoid, tree, grass, monophosphoryl lipid A, MPL®