4149 Down Regulation of Allergic Inflammation with Allergy Vaccine Timpol In A Murine Model of Asthma

Wednesday, 7 December 2011: 13:30 - 00:00
Bacalar (Cancún Center)

Igor Shilovskiy , National Research Center - Institute of Immunology, Moscow, Russia

Alexander Babakhin , National Research Center - Institute of Immunology, Moscow, Russia

Musa Khaitov , National Research Center - Institute of Immunology, Moscow, Russia

Alexander Martinov , National Research Center - Institute of Immunology, Moscow, Russia

Background: Despite of 100 years using allergen-specific immunotherapy (ASIT) it needs to be improved. Timpol is a novel allergovaccine prepared by conjugation of Tymothy grass pollen (G6) allergoid and immunomodulator Polyoxidonium. The purpose of this study was to assess the efficacy of experimental ASIT with Timpol to suppress allergic inflammation in IgE-mediated murine model of asthma (MMA).

Methods: Female BALB/c mice were sensitized with seven i.p. injections of 1 mg/kg (taken in protein equivalents) of G6-extract and later on were challenged with eight intranasal applications (IA) of G6 in concentration of 10 mg/ml. Between sensitization and IA periods different groups of mice were treated with s.c. injections of Timpol in total doses: 4, 40 400, and 4000 μg/kg. Two control groups obtained ASIT with either G6 (total dose 19.7 mg/kg) or saline only. The levels of serum anti-G6 IgE/IgG antibodies (Ab) were detected by ELISA. After IA lungs were taken for histological examination, bronchial hyper-reactivity to metacholine was assessed by non-invasive pneumography and cell composition in bronchoalveolar lavage (BAL) was evaluated by microscopy.

Results: Anti-G6 IgE Ab were elevated in all groups in the beginning of ASIT and slightly decreased at the end of treatment. After IA the levels of anti-G6 IgE in groups treated with G6 and Timpol (doses 40 and 400 µg/kg) were similar to that of control group (saline). Anti-G6 IgG Ab have been increasing during ASIT in all groups. The highest level of anti-G6 IgG was noticed after IA in groups treated with Timpol (doses 4 and 40 µg/kg). All groups of mice treated with Timpol demonstrated reduction of allergic inflammation in lungs in comparison to the control group (saline). ASIT with Timpol in doses 4 and 40 µg/kg reduced eosinophil and inflammatory cell count in BAL. ASIT with Timpol in doses 4, 40 and 400 µg/kg demonstrated improvement of lung function assessed by pneumography.

Conclusions: Data obtained support the conception that ASIT with Timpol especially in dose 40 µg/kg may be effective approach for treatment of mild asthma in humans.