Allergen-specific nasal IgG antibodies induced by vaccination with genetically modified allergens are associated with reduced nasal allergen sensitivity - 18/08/11

Doi : 10.1016/j.jaci.2005.04.003

Jürgen Reisinger, MSc ^a, Friedrich Horak, MD ^a, Gabrielle Pauli, MD ^e, Marianne van Hage, MD ^d, Oliver Cromwell, PhD ^f, Franz König ^c, Rudolf Valenta, MD ^b, Verena Niederberger, MD ^a,^⁎
^a From the Department of Otorhinolaryngology
^b Department of Pathophysiology, Center for Physiology and Pathophysiology, Vienna General Hospital
^c Department of Medical Statistics, Medical University of Vienna
^d Department of Medicine, Clinical Immunology and Allergy Unit, Karolinska Institutet and Hospital, Stockholm
^e Service de Pneumologie, Hôpitaux Universitaires de Strasbourg
^f Allergopharma Joachim-Ganzer KG, Reinbek

Reprint requests: Verena Niederberger, MD, Department of Otorhinolaryngology, Vienna General Hospital, AKH, Medical University of Vienna, Waehringer Guertel 18-20, A-1090 Vienna, Austria.

Vienna, Austria, Stockholm, Sweden, Strasbourg, France, and Reinbek, Germany

Abstract

Background

We have performed a double-blind, placebo-controlled injection immunotherapy study with genetically modified derivatives of the major birch pollen allergen, Bet v 1 (Bet v 1–trimer, Bet v 1–fragments).

Objective

To investigate whether vaccination with genetically modified allergens induces allergen-specific antibodies in nasal secretions and to study whether these antibodies affect nasal allergen sensitivity.

Methods

A randomly picked subgroup of patients (n=23; placebo, n=10; trimer, n=10; fragments, n=3) was subjected to an extensive analysis of serum samples and nasal lavage fluids and to nasal provocation testing. Bet v 1–specific IgG_1-4 and IgA antibodies were determined in serum samples obtained before and after vaccination, after the birch pollen season, and 1 year after start of vaccination as well as in nasal lavage fluids obtained after the birch pollen season and 1 year after start of vaccination by ELISA. Nasal sensitivity to natural, birch pollen–derived Bet v 1 was determined by active anterior rhinomanometry after the birch pollen season and 1 year after start of vaccination.

Results

Vaccination with genetically modified Bet v 1 derivatives, but not with placebo, induced Bet v 1–specific IgG₁, IgG₂, and IgG₄, and low IgA antibodies in serum, which also appeared in nasal secretions, but no IgG₃ antibodies. The levels of therapy-induced Bet v 1–specific IgG₄ antibodies in nasal secretions were significantly (P < .05) associated with reduced nasal sensitivity to natural, birch pollen–derived Bet v 1 as objectively determined by controlled nasal provocation experiments.

Conclusion

Our data demonstrate that vaccination with genetically modified allergens induces IgG antibody responses against the corresponding natural allergen not only in serum but also in mucosal fluids, where they may protect against allergen-induced inflammation.

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Key words : Allergen-specific immunotherapy, IgG antibodies, genetically modified allergens, nasal provocation

Abbreviation used : r