Abstract
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.
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All data are included in the Supplementary Information or available from the authors, as are unique reagents used in this Article. The raw numbers for charts and graphs are available in the Source Data file whenever possible. Any further requests can be addressed to the corresponding author. Source data are provided with this paper.
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Acknowledgements
E.R.dT acknowledges support from DTU Discovery Grant, DTU Proof of Concept, Innovation Fund Denmark InnoExplorer [2071-00021] and DFF Inge Lehmann program [4306-00008B]. A.H.L. acknowledges support from the European Research Council (ERC) under the European Union’s Horizon 2020 research and innovation programme [850974 and 101112851] and the Villum Foundation [00025302]. K.H.J. acknowledges support from Lundbeckfonden [R347-2020-2174] and Arvid Nilssons Foundation. M.T.V. acknowledges support from the Spanish Ministry of Science and Education [PID2020-116692RB-I00]. CM holds a “Nicolas Monardes” research contract by the Andalusian Regional Ministry Health (RC0004-2021). JLP acknowledges grants RYC2021-034536-I and CNS2023-145619 funded by MICIU/AEI/10.13039/501100011033 and by European Union NextGenerationEU/PRTR. CJA acknowledges grant RYC2023-043687-I funded by MICIU/AEI/10.13039/501100011033 and by ESF + .
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E.R.dT., K.H.J., A.H.L., and T.P.J. conceptualized the study. E.R.dT., K.H.J., M.V., T.P.J., M.M., R.M., C.M. and J.K.C. developed the methodology. E.R.dT., M.M., J.P.B., J.T., R.M., J.K.C., K.H.J., L.F.V., H.H.E., U.F.F., J.L.P., C.J.A., and B.M. carried out the investigation. K.H.J., E.R.dT., J.V.K., M.M., and J.P.B. handled data analysis and visualization. E.R.dT., A.H.L., K.H.J., and M.V. were responsible for funding acquisition. E.R.dT took the lead in project administration, while E.R.dT, A.H.L., O.L., V.C., J.B., M.P., S.R.H., and M.V. provided resources. E.R.dT., K.H.J., and A.H.L. supervised. E.R.dT., A.H.L., M.M., and K.H.J. wrote the original draft, and all authors contributed to the review and editing process.
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E.R.dT., A.H.L., and T.P.J. are named inventors on a patent application (WO2023242436) based on the work presented in this paper. The rest of the authors declare no competing interests.
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Møiniche, M., Johansen, K.H., Parrón-Ballesteros, J. et al. An mRNA-delivered consensus allergen induces a neutralizing IgG response against food and pollen allergens. Nat Commun (2026). https://doi.org/10.1038/s41467-026-69134-4
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DOI: https://doi.org/10.1038/s41467-026-69134-4
