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ResearchIn-Press PreviewImmunologyInflammation Open Access | 10.1172/JCI194080

Allergen-Specific mRNA-Lipid Nanoparticle Therapy for Prevention and Treatment of Experimental Allergy in Mice

Yrina Rochman,1 Michael Kotliar,1 Andrea M. Klingler,1 Mark Rochman,1 Mohamad-Gabriel Alameh,3 Jilian R. Melamed,3 Garrett A. Osswald,1 Julie M. Caldwell,1 Jennifer M. Felton,1 Lydia E. Mack,1 Julie Hargis,4 Ian P. Lewkowich,4 Artem Barski,5 Drew Weissman,6 and Marc E. Rothenberg1

1Division of Allergy and Immunology, Cincinnati Children’s Hospital Medical Center, Cincinnati, United States of America

2Division of Allergy and Immunology, Cincinnati Children’s Hospital Medical Center, Cinicnnati, United States of America

3Department of Medicine, University of Pennsylvania, Perelman School of Medicine, Philadelphia, United States of America

4Division of Immunobiology, Cincinnati Children’s Hospital Medical Center, Cincinnati, United States of America

5Division of Allergy and Immunology, Cincinnati Children's Hospital Medical Center, Cincinnati, United States of America

6Department of Medicine, University of Pennsylvania, Philadelphia, United States of America

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1Division of Allergy and Immunology, Cincinnati Children’s Hospital Medical Center, Cincinnati, United States of America

2Division of Allergy and Immunology, Cincinnati Children’s Hospital Medical Center, Cinicnnati, United States of America

3Department of Medicine, University of Pennsylvania, Perelman School of Medicine, Philadelphia, United States of America

4Division of Immunobiology, Cincinnati Children’s Hospital Medical Center, Cincinnati, United States of America

5Division of Allergy and Immunology, Cincinnati Children's Hospital Medical Center, Cincinnati, United States of America

6Department of Medicine, University of Pennsylvania, Philadelphia, United States of America

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1Division of Allergy and Immunology, Cincinnati Children’s Hospital Medical Center, Cincinnati, United States of America

2Division of Allergy and Immunology, Cincinnati Children’s Hospital Medical Center, Cinicnnati, United States of America

3Department of Medicine, University of Pennsylvania, Perelman School of Medicine, Philadelphia, United States of America

4Division of Immunobiology, Cincinnati Children’s Hospital Medical Center, Cincinnati, United States of America

5Division of Allergy and Immunology, Cincinnati Children's Hospital Medical Center, Cincinnati, United States of America

6Department of Medicine, University of Pennsylvania, Philadelphia, United States of America

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1Division of Allergy and Immunology, Cincinnati Children’s Hospital Medical Center, Cincinnati, United States of America

2Division of Allergy and Immunology, Cincinnati Children’s Hospital Medical Center, Cinicnnati, United States of America

3Department of Medicine, University of Pennsylvania, Perelman School of Medicine, Philadelphia, United States of America

4Division of Immunobiology, Cincinnati Children’s Hospital Medical Center, Cincinnati, United States of America

5Division of Allergy and Immunology, Cincinnati Children's Hospital Medical Center, Cincinnati, United States of America

6Department of Medicine, University of Pennsylvania, Philadelphia, United States of America

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1Division of Allergy and Immunology, Cincinnati Children’s Hospital Medical Center, Cincinnati, United States of America

2Division of Allergy and Immunology, Cincinnati Children’s Hospital Medical Center, Cinicnnati, United States of America

3Department of Medicine, University of Pennsylvania, Perelman School of Medicine, Philadelphia, United States of America

4Division of Immunobiology, Cincinnati Children’s Hospital Medical Center, Cincinnati, United States of America

5Division of Allergy and Immunology, Cincinnati Children's Hospital Medical Center, Cincinnati, United States of America

6Department of Medicine, University of Pennsylvania, Philadelphia, United States of America

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1Division of Allergy and Immunology, Cincinnati Children’s Hospital Medical Center, Cincinnati, United States of America

2Division of Allergy and Immunology, Cincinnati Children’s Hospital Medical Center, Cinicnnati, United States of America

3Department of Medicine, University of Pennsylvania, Perelman School of Medicine, Philadelphia, United States of America

4Division of Immunobiology, Cincinnati Children’s Hospital Medical Center, Cincinnati, United States of America

5Division of Allergy and Immunology, Cincinnati Children's Hospital Medical Center, Cincinnati, United States of America

6Department of Medicine, University of Pennsylvania, Philadelphia, United States of America

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1Division of Allergy and Immunology, Cincinnati Children’s Hospital Medical Center, Cincinnati, United States of America

2Division of Allergy and Immunology, Cincinnati Children’s Hospital Medical Center, Cinicnnati, United States of America

3Department of Medicine, University of Pennsylvania, Perelman School of Medicine, Philadelphia, United States of America

4Division of Immunobiology, Cincinnati Children’s Hospital Medical Center, Cincinnati, United States of America

5Division of Allergy and Immunology, Cincinnati Children's Hospital Medical Center, Cincinnati, United States of America

6Department of Medicine, University of Pennsylvania, Philadelphia, United States of America

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1Division of Allergy and Immunology, Cincinnati Children’s Hospital Medical Center, Cincinnati, United States of America

2Division of Allergy and Immunology, Cincinnati Children’s Hospital Medical Center, Cinicnnati, United States of America

3Department of Medicine, University of Pennsylvania, Perelman School of Medicine, Philadelphia, United States of America

4Division of Immunobiology, Cincinnati Children’s Hospital Medical Center, Cincinnati, United States of America

5Division of Allergy and Immunology, Cincinnati Children's Hospital Medical Center, Cincinnati, United States of America

6Department of Medicine, University of Pennsylvania, Philadelphia, United States of America

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1Division of Allergy and Immunology, Cincinnati Children’s Hospital Medical Center, Cincinnati, United States of America

2Division of Allergy and Immunology, Cincinnati Children’s Hospital Medical Center, Cinicnnati, United States of America

3Department of Medicine, University of Pennsylvania, Perelman School of Medicine, Philadelphia, United States of America

4Division of Immunobiology, Cincinnati Children’s Hospital Medical Center, Cincinnati, United States of America

5Division of Allergy and Immunology, Cincinnati Children's Hospital Medical Center, Cincinnati, United States of America

6Department of Medicine, University of Pennsylvania, Philadelphia, United States of America

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1Division of Allergy and Immunology, Cincinnati Children’s Hospital Medical Center, Cincinnati, United States of America

2Division of Allergy and Immunology, Cincinnati Children’s Hospital Medical Center, Cinicnnati, United States of America

3Department of Medicine, University of Pennsylvania, Perelman School of Medicine, Philadelphia, United States of America

4Division of Immunobiology, Cincinnati Children’s Hospital Medical Center, Cincinnati, United States of America

5Division of Allergy and Immunology, Cincinnati Children's Hospital Medical Center, Cincinnati, United States of America

6Department of Medicine, University of Pennsylvania, Philadelphia, United States of America

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1Division of Allergy and Immunology, Cincinnati Children’s Hospital Medical Center, Cincinnati, United States of America

2Division of Allergy and Immunology, Cincinnati Children’s Hospital Medical Center, Cinicnnati, United States of America

3Department of Medicine, University of Pennsylvania, Perelman School of Medicine, Philadelphia, United States of America

4Division of Immunobiology, Cincinnati Children’s Hospital Medical Center, Cincinnati, United States of America

5Division of Allergy and Immunology, Cincinnati Children's Hospital Medical Center, Cincinnati, United States of America

6Department of Medicine, University of Pennsylvania, Philadelphia, United States of America

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1Division of Allergy and Immunology, Cincinnati Children’s Hospital Medical Center, Cincinnati, United States of America

2Division of Allergy and Immunology, Cincinnati Children’s Hospital Medical Center, Cinicnnati, United States of America

3Department of Medicine, University of Pennsylvania, Perelman School of Medicine, Philadelphia, United States of America

4Division of Immunobiology, Cincinnati Children’s Hospital Medical Center, Cincinnati, United States of America

5Division of Allergy and Immunology, Cincinnati Children's Hospital Medical Center, Cincinnati, United States of America

6Department of Medicine, University of Pennsylvania, Philadelphia, United States of America

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1Division of Allergy and Immunology, Cincinnati Children’s Hospital Medical Center, Cincinnati, United States of America

2Division of Allergy and Immunology, Cincinnati Children’s Hospital Medical Center, Cinicnnati, United States of America

3Department of Medicine, University of Pennsylvania, Perelman School of Medicine, Philadelphia, United States of America

4Division of Immunobiology, Cincinnati Children’s Hospital Medical Center, Cincinnati, United States of America

5Division of Allergy and Immunology, Cincinnati Children's Hospital Medical Center, Cincinnati, United States of America

6Department of Medicine, University of Pennsylvania, Philadelphia, United States of America

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1Division of Allergy and Immunology, Cincinnati Children’s Hospital Medical Center, Cincinnati, United States of America

2Division of Allergy and Immunology, Cincinnati Children’s Hospital Medical Center, Cinicnnati, United States of America

3Department of Medicine, University of Pennsylvania, Perelman School of Medicine, Philadelphia, United States of America

4Division of Immunobiology, Cincinnati Children’s Hospital Medical Center, Cincinnati, United States of America

5Division of Allergy and Immunology, Cincinnati Children's Hospital Medical Center, Cincinnati, United States of America

6Department of Medicine, University of Pennsylvania, Philadelphia, United States of America

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1Division of Allergy and Immunology, Cincinnati Children’s Hospital Medical Center, Cincinnati, United States of America

2Division of Allergy and Immunology, Cincinnati Children’s Hospital Medical Center, Cinicnnati, United States of America

3Department of Medicine, University of Pennsylvania, Perelman School of Medicine, Philadelphia, United States of America

4Division of Immunobiology, Cincinnati Children’s Hospital Medical Center, Cincinnati, United States of America

5Division of Allergy and Immunology, Cincinnati Children's Hospital Medical Center, Cincinnati, United States of America

6Department of Medicine, University of Pennsylvania, Philadelphia, United States of America

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Published September 23, 2025 - More info

J Clin Invest. https://doi.org/10.1172/JCI194080.
Copyright © 2025, Rochman et al. This work is licensed under the Creative Commons Attribution 4.0 International License. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
Published September 23, 2025 - Version history
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Abstract

Allergic diseases have reached epidemic proportions globally, calling attention to the need for better treatment and preventive approaches. Herein, we developed allergen-encoding messenger RNA (mRNA) lipid nanoparticle (LNP) strategies for both therapy and prevention of allergic responses. Immunization with allergen-encoded mRNA-LNPs modulated T cell differentiation, inhibiting the generation of T helper type 2 (Th2) and type 17 (Th17) cells upon allergen exposure in experimental asthma models induced by ovalbumin (OVA), and naturally occurring house dust mite (HDM) and the major HDM allergen Der p1. Allergen-specific mRNA-LNP treatment attenuated clinicopathology in both preventive and established allergy models, including reduction in eosinophilia, mucus production, and airway hypersensitivity, while enhancing production of allergen-specific IgG antibodies and maintaining low IgE levels. Additionally, allergen-specific mRNA-LNP vaccines in mice elicited a CD8+CD38+KLRG- T cell response as seen following SARS-CoV-2 mRNA vaccination in human, underscoring a conserved immune mechanism across species, regardless of the mRNA-encoded protein. Notably, mRNA-LNP vaccination in combination with an mTOR inhibitor reduced the CD8+ T cell response without affecting the vaccine-induced anti-allergic effect in the preventive model of asthma. This technology renders allergen-specific mRNA-LNP therapy as a promising approach for prevention and treatment of allergic diseases.

Graphical Abstract
graphical abstract
Supplemental material

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View Table4_DEG_Interstitial MP

View Table5_DEG_Plasma cells

View Table6_DEG_Dendritic cells

Version history
  • Version 1 (September 23, 2025): In-Press Preview
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