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.