A hypoallergenic variant of Der p 1 as a candidate for mite allergy vaccines.

Abstract

BACKGROUND:

Recombinant hypoallergens that display reduced allergenicity but retain T-cell reactivity represent promising candidates to improve the safety and efficacy of allergen-specific vaccines or immunotherapy.

OBJECTIVE:

The current study reports the immunologic characterization of a hypoallergenic variant of the major mite allergen Der p 1.

METHODS:

The recombinant proform of Der p 1 (ProDer p 1) was expressed in Escherichia coli (ProDer p 1 coli), purified and characterized at the level of its secondary structure, and IgE and T-cell reactivities. Moreover, the prophylactic potential of ProDer p 1 coli vaccinations was evaluated in a murine Der p 1 sensitization model.

RESULTS:

After purification and refolding, ProDer p 1 coli remained aggregated with a higher beta-sheet content and altered Der p 1 conformational epitopes compared with the correctly folded monomeric ProDer p 1 produced in Chinese hamster ovary cells. Both ProDer p 1 forms were able to retain the Der p 1-specific T-cell reactivity but direct ELISA, competitive inhibition, and rat basophil leukemia assays clearly showed that ProDer p 1 coli displays a very weak IgE reactivity. Mice vaccinations with aggregated ProDer p 1 adjuvanted with alum induced a T(H)1-biased immune response that prevented the subsequent allergic response after Der p 1 sensitization and airway challenge with aerosolized mite extracts. Furthermore, ProDer p 1 coli treatment inhibited the development of airway eosinophilia and airway hyperresponsiveness to inhaled methacholine.

CONCLUSION:

Aggregated forms of Der p 1 could represent hypoallergens suitable for the prevention of mite allergy.

• Authors: David Walgraffe, Christel Mattéotti, Mohamed El Bakkoury, Lida Garcia, Céline Marchand, Dominique Bullens, Michel Vandenbranden, Alain Jacquet
• Journal: The Journal of allergy and clinical immunology (J Allergy Clin Immunol) Vol. 123 Issue 5 Pg. 1150-6 (May 2009) ISSN: 1097-6825 [Electronic] United States
• PMID: 19152967 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Allergens
• Antigens, Dermatophagoides
• Arthropod Proteins
• Bronchoconstrictor Agents
• Interleukin-5
• Recombinant Proteins
• Vaccines
• Methacholine Chloride
• Immunoglobulin E
• Interferon-gamma
• Cysteine Endopeptidases
• Dermatophagoides pteronyssinus antigen p 1

Topics

• Allergens (immunology)
• Animals
• Antigens, Dermatophagoides (genetics, isolation & purification, pharmacology)
• Arthropod Proteins
• Basophils (drug effects, immunology, metabolism)
• Bronchial Hyperreactivity (immunology, prevention & control)
• Bronchoconstrictor Agents (pharmacology)
• Cell Line, Tumor
• Cloning, Molecular
• Cysteine Endopeptidases
• Disease Models, Animal
• Eosinophilia (immunology, prevention & control)
• Female
• Humans
• Hypersensitivity (immunology, prevention & control)
• Immunoglobulin E (blood)
• Interferon-gamma (biosynthesis, immunology)
• Interleukin-5 (biosynthesis, immunology)
• Methacholine Chloride (pharmacology)
• Mice
• Mice, Inbred BALB C
• Pyroglyphidae (immunology)
• Rats
• Recombinant Proteins (genetics, immunology)
• T-Lymphocytes (drug effects, immunology, metabolism)
• Vaccines (immunology)