Allergen‐specific immunotherapy with a monophosphoryl lipid A‐adjuvanted vaccine: reduced seasonally boosted immunoglobulin E production and inhibition of basophil histamine release by therapy‐induced blocking antibodies

Summary Background Allergen‐specific immunotherapy represents a causal form of treatment for IgE‐mediated allergies. The allergen extract‐based analyses of immunotherapy‐induced effects yielded highly controversial results regarding a beneficial role of therapy‐induced IgG antibodies. Objective We analysed allergen‐specific IgE, IgG subclass, and IgM responses in patients treated with a grass pollen allergy vaccine adjuvanted with monophosphoryl lipid A (MPL), a Th1‐inducing agent, and in a placebo group using recombinant timothy grass pollen allergen molecules (rPhl p 1, rPhl p 2, rPhl p 5). Results The strong induction of allergen‐specific IgG 1 and IgG 4 antibodies observed only in the actively treated group was associated with significant clinical improvement. Therapy‐induced allergen‐specific IgM and IgG 2 responses were also noted in several actively treated patients. An inhibition of allergen‐dependent basophil histamine release was only obtained with sera containing therapy‐induced allergen‐specific IgG, but not with sera obtained before therapy or from placebo‐treated patients. Moreover, patients with therapy‐induced allergen‐specific IgG antibodies showed a reduced induction of allergen‐specific IgE responses during seasonal grass pollen exposure. Conclusion Successful immunotherapy with the MPL‐adjuvanted grass pollen allergy vaccine is associated with the production of allergen‐specific IgG antibodies. These blocking antibodies may have protective effects by inhibiting immediate‐type reactions and systemic increases of IgE responses caused by seasonal allergen exposure.