An mRNA-delivered consensus allergen induces a neutralizing IgG response against food and pollen allergens

Cross-allergies affect a significant proportion of the population, and contribute to detrimental health and socioeconomic impacts, yet allergen immunotherapies often target a single allergen source disregarding cross-reactive allergens from other sources. Here we introduce an immunization approach developed for improved desensitization in cross-allergic patients using a consensus allergen (cnsLTP1), which contains orthologous non-specific lipid transfer proteins (nsLTP) derived from relevant fruit and pollen allergens. In BALB/c mice, vaccination via either mRNA-lipid nanoparticle (LNP) vehicle or traditional protein formulation induces cnsLTP1-specific IgGs capable of recognizing and binding to multiple nsLTPs. These IgGs block allergen binding by patient serum IgEs and prevent humanized rat basophil degranulation in vitro. Meanwhile, in an allergic mouse model, the mRNA-LNP formulation is tolerated and induces allergen-specific IgG responses but does not ameliorate subsequent allergen challenge responses. Regardless, this cross-allergen mRNA-LNP-based immunotherapy may have translation value once route of administration, formulation and/or dosing are optimized. Therapy to allergy often targets a specific allergen without addressing cross-reactivity. Here the authors develop a consensus, cross-reactive allergen, use mRNA-lipid nanoparticle immunization to induce specific, neutralizing IgG responses, but find no therapeutic effects in mouse allergy models, hinting the need for further optimization prior to translation.