Multivalent paediatric allergy vaccines protect against allergic anaphylaxis in mice.

BACKGROUND: Almost a quarter of the world population suffers from IgE-mediated allergies. T cells and IgG-producing B cells can produce protection, but treatment for disease is laborious with unsatisfactory patient compliance. OBJECTIVE: We sought to identify whether paediatric allergy vaccines affected later allergen sensitization and onset of disease when used prophylactically. METHODS: A murine model of anaphylaxis was applied. Mice were first immunized with monovalent or multivalent allergy vaccines that also contained aluminium hydroxide and CpG oligodeoxynucleotide as adjuvants. Later, the mice were sensitized by multiple low-dose injections of aluminium-adsorbed allergen. After a dormant period, the mice were challenged systemically with high-dose allergen, and the clinical signs of anaphylaxis were recorded. Throughout the immunization and sensitization periods, blood was collected for serological testing. RESULTS: Immunization with allergy vaccines produced antigen-specific protection against sensitization as measured by systemic anaphylaxis in mice. The long-term effect was observed both after juvenile (5-6 weeks) and neonatal (7 days) vaccination. Monovalent and pentavalent vaccines were protective to a similar level. Protection was associated with increased secretion of IgG2a and production of IFN-γ. Protection could also be transferred to sensitized mice via serum or via CD25-positive CD4 T cells. CONCLUSION AND CLINICAL RELEVANCE: Prophylactic and multivalent allergy vaccines in juvenile and neonatal mice protected against later sensitization and anaphylaxis. Such treatment may provide a rational measure for future management of allergen-related diseases and their strong socio-economic impact on daily life.

The contact sensitizer diphenylcyclopropenone has adjuvant properties in mice and potential application in epicutaneous immunotherapy.

BACKGROUND: Epicutaneous vaccination has gained increasing interest during the past decade as it offers a safe, needle-free, and patient-friendly alternative to invasive vaccine administrations. Recently, the safety and early efficacy of epicutaneous immunotherapy were also demonstrated in patients with hay fever, as an alternative to conventional subcutaneous allergen-specific immunotherapy (SCIT). One major challenge to epicutaneous vaccination is the barrier function of the stratum corneum, which must be overcome either by abrasive methods or by hydration. Such barrier function of the stratum corneum also hampers the use of common adjuvants used to enhance the efficacy of vaccination. METHODS: In a mouse model of allergy, we tested the adjuvant potential of diphenylcyclopropenone (DCP), a strong contact sensitizer, which is currently used for the treatment of a T cell-mediated hair loss disease (alopezia areata). RESULTS: Diphenylcyclopropenone enhanced antigen-specific IgG2a antibody responses as well as IL-10 cytokine production after epicutaneous immunization with ovalbumin (OVA). Epicutaneous allergen-specific immunotherapy (EPIT) with OVA and DCP also protected sensitized mice from anaphylaxis and asthma. The protective effect was more robust than that of conventional SCIT, which did not significantly alleviate the symptoms of allergy in the murine models of anaphylaxis and asthma. CONCLUSIONS: This preclinical study confirmed previous clinical data that have demonstrated the potential of the skin as a target for allergen immunotherapy. The study also suggests that epicutaneous immunization or immunotherapy can be improved when an appropriate adjuvant such as DCP is used.