Immunotherapy of type-1 allergies with virus-like particles and CpG-motifs

Abstract

Immunotherapy of type-I-allergies is regarded as the most efficient treatment option besides allergen avoidance. Different forms of allergen preparations are used as well as different routes of application. Virus-like particles represent a potent vaccine platform with proven immunogenicity and clinical efficacy. The addition of toll-like receptor ligands and/or depot-forming adjuvants further enhances immune cell activation. This article will focus on the function of virus-like particles loaded with DNA rich in CpG-motifs and discuss clinical experience in treatment of allergic rhinitis. Evidence will be presented that clinically effective treatment can be obtained even in the absence of allergens. Results encourage further investigation of virus-like particles and CpG-motifs in immunotherapy, either as a stand alone product, or as adjuvants for allergen-specific immunotherapy.

Keywords::

• allergen
• asthma
• CpG
• immunotherapy
• rhinitis
• toll-like receptor
• virus-like particle

Financial & competing interests disclosure

This work has been supported by the Center for Rhinology and Allergology, Wiesbaden, Germany (L Klimek), Saiba GmbH, Rämismühle, Switzerland (MF Bachmann), Department of Dermatology, USZ, Zürich, Schweiz (MF Bachmann, G Senti and T Kündig). L Klimek received sponsorship and grants for performing clinical trials, advice and writing from ALK-Abello, Danmark, Allergopharma, Germany, Artu-Biologicals, Netherlands, Bencard, Great Britain, Bionorica, Germany, Biomay, Austria, Cassella, Germany, Cytos, Switzerland, Dr. Pfleger, Germany, HAL, Netherlands, Hartington, Spain, GSK, Great Britain, Infectopharm, Germany, Leti, Spain, Lofarma, Italy, MEDA, Germany, Novartis, Switzerland, Roxall, Germany; Springer Publishers, Germany, Schattauer Publishers, Germany. He is a member of DGHNO; ÄDA; Deutsche Akademie für HNO-Heilkunde; Deutsche Akademie für Allergologie und klinische Immunologie; HNO-BV; GPA; EAACI; ARS; AACI; WAO; Medical Faculty Mannheim, University of Heidelberg; Medical Faculty, Mainz University. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

Key issues

• Current allergen immunotherapy requires too many allergen administrations and has a risk of allergic side effects.

• CG-rich bacterial DNA (CpGs) represents a potent Th1-inducing adjuvant.

• Virus-like particles (VLPs) can be used to package, stabilize and target CpGs to lymphatic organs and dendritic cells.

• Allergens can readily be coupled to the surface of VLPs, making them look like a virus to the immune system.

• VLPs filled with CpGs can also be used as an adjuvant which is mixed together with allergens.

• VLPs filled with CpGs, even without allergens, have been found to ameliorate allergy symptoms.

• CpGs are potent immunomodulators with toll-like receptor 9 expressed in plasmacytoid DCs , B cells, mast cells, neutrophils, eosinophils and basophils.

• More research needs to compare the therapeutic potency of allergen-coupled VLPs, allergen admixed to VLPs and CpG-loaded VLPs without allergens.