Regulation of the human immune response to ragweed pollen by immunotherapy. A controlled trial comparing the effect of immunosuppressive peptic fragments of short ragweed with standard treatment

Abstract

A new allergenic preparation consisting of peptic fragments of short ragweed has been tested for its clinical effectiveness. Such enzymatically derived fragments have been shown in prior murine studies to retain the T epitopes of the original allergen but to have a severe reduction in the number of B epitopes. Three groups of ragweed hayfever patients were placed on pre-seasonal immunotherapy. One group received a conventional ragweed preparation that had been enriched for antigen E (Amb a I), designated as Pool 2. The second group was given fragments of Pool 2 (fSRW) prepared by peptic digestion and the third group was injected with histamine as a placebo. Groups treated with the fSRW and Pool 2 had significantly reduced symptom-medication scores compared with the placebo-treatment group. However, fSRW-treated patients fared significantly better than Pool 2 patients (P less than 0.02). fSRW injections caused a significant rise in preseasonal specific IgG, antibodies as well as suppression of the seasonal anamnestic specific IgE increase. Similar, but not quite as marked changes occurred with Pool 2 treatment. fSRW was well tolerated and non-toxic. Thus, allergen modification by enzymatic degradation, as demonstrated here, appears to be a promising new approach for allergen immunotherapy.

Four Recombinant Isoforms of Cor a 1, the Major Allergen of Hazel Pollen, Show Different Reactivities with Allergen‐specific T‐lymphocyte Clones

“…Considering the use of recombinant allergens for immunotherapy it would certainly be necessary to identify immunodominant isoforms. Moreover, hyposensitation with a mixture of highly antigenic recombinant isoforms of one allergenic protein, or multiple allergen-derived peptides [22,231 with the characteristics of T-cell but not B-cell epitopes, should be considered as another approach to affect T-cell reactivity.…”

“…The knowledge of cross-reacting T-cell epitopes of allergens will certainly have impact on the choice of immunodominant isoforms of allergens for immunotherapy. Moreover, in the future, this information will be essential for the design of peptides which represent relevant T-cell epitopes and are capable of modulating the T-cell response of allergic patients [22,231.…”

Developments in allergen‐specific immunotherapy: from allergen extracts to allergy vaccines bypassing allergen‐specific immunoglobulin E and T cell reactivity

“…The IgE reactivity of the allergen extracts was reduced by denaturation using aldehydes resulting in allergoids [69,70,77,78], by proteolysis [79][80][81] or by conjugation of the extracts to chemical groups (e.g. using mPEG) [82,83].…”

Immunotherapy as an effective tool in allergy treatment

“…Most immunotherapy studies investigated the efficacy of pollen allergies. These studies can be subdivided into 13 studies (5,7,9,11,12,15,17,19,22,32,35,36,39) investigating ragweed allergy (nine showing clinically relevant efficacy, i.e., symptom/medication scores diminished by >30% in the actively treated). Fifteen studies investigated the efficacy of immunotherapy in grass-pollen allergy (8,13,16,18,20,21,23,25,30,34,37,38,40,44,47), of which 14 proved efficacy.…”