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.
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 IgG1 and IgG4 antibodies observed only in the actively treated group was associated with significant clinical improvement. Therapy-induced allergen-specific IgM and IgG2 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.


CONCLUSIONS
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.
Mothes
N
N
Department of Pathophysiology, Vienna General Hospital, University of Vienna, Vienna, Austria.
Heinzkill
M
M
Drachenberg
K J
KJ
Sperr
W R
WR
Krauth
M T
MT
Majlesi
Y
Y
Semper
H
H
Valent
P
P
Niederberger
V
V
Kraft
D
D
Valenta
R
R
D000276:Adjuvants, Immunologic / Q000627:therapeutic use*; D000485:Allergens / Q000276:immunology*; D001491:Basophils / Q000276:immunology; D004311:Double-Blind Method; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D006636:Histamine Release / Q000276:immunology; D006801:Humans; D006969:Hypersensitivity, Immediate / Q000276:immunology / Q000517:prevention & control; D007073:Immunoglobulin E / Q000096:biosynthesis* / Q000276:immunology; D007074:Immunoglobulin G / Q000096:biosynthesis / Q000276:immunology; D007075:Immunoglobulin M / Q000096:biosynthesis / Q000276:immunology; D007167:Immunotherapy / Q000379:methods*; D008050:Lipid A / Q000031:analogs & derivatives* / Q000276:immunology / Q000627:therapeutic use*; D031784:Phleum / Q000276:immunology; D011058:Pollen / Q000276:immunology; D012621:Seasons; D014612:Vaccines / Q000627:therapeutic use
D000276:Adjuvants, Immunologic; D000485:Allergens; D007074:Immunoglobulin G; D007075:Immunoglobulin M; D008050:Lipid A; D014612:Vaccines; D007073:Immunoglobulin E; C048436:monophosphoryl lipid A