Nebulization of an mRNA-encoded monoclonal antibody for passive immunization of foals against Rhodococcus equi.
Abstract: Inhalation of Rhodococcus equi causes severe pneumonia in humans and animals worldwide, most commonly affecting horse foals. The standard for preventing R. equi pneumonia in foals is transfusion of hyperimmune plasma, which is expensive and carries the risk of adverse effects. Our goal was to passively immunize foals against R. equi by nebulizing mRNA encoding an equine monoclonal antibody (mAb) against the virulence-associated protein A (VapA) directly into the lungs. VapA-specific memory B cells from an immunized horse were used to identify and select the sequence for an equine immunoglobulin (Ig)G1 mAb. In vitro-transcribed mRNA encoding this sequence expressed full-length, VapA-specific mAbs in vitro and safely and effectively produced intrapulmonary mAb in foals for at least 5 days following nebulization. These findings establish a platform to generate mRNA-encoded mAbs for immunotherapeutic and immunoprophylactic applications in horses and demonstrate the feasibility of delivering nebulized mRNA-mAb for intrapulmonary mAb expression in neonates.
Copyright © 2025 The American Society of Gene and Cell Therapy. Published by Elsevier Inc. All rights reserved.
Publication Date: 2025-06-14 PubMed ID: 40518672DOI: 10.1016/j.ymthe.2025.06.025Google Scholar: Lookup
The Equine Research Bank provides access to a large database of publicly available scientific literature. Inclusion in the Research Bank does not imply endorsement of study methods or findings by Mad Barn.
- Journal Article
Summary
This research summary has been generated with artificial intelligence and may contain errors and omissions. Refer to the original study to confirm details provided. Submit correction.
This study explores a novel, less costly and potentially safer method of protecting young horses from Rhodococcus equi pneumonia. The researchers used an equine monoclonal antibody, delivered via nebulization, to stimulate a defensive immune response in foals.
Research Objectives and Methods
- The aim of the study was to create a new way to protect foals from R. equi pneumonia, a severe respiratory disease affecting foals and humans worldwide.
- Traditionally, foals are protected against this disease by using hyperimmune plasma, a technique which can be costly and has potential side effects.
- The researchers wanted to use mRNA encoding a specific monoclonal antibody (mAb) derived from horses and deliver it directly into the lungs of the foals through nebulization.
Procedure and Findings
- The research group used memory B-cells from a horse immunized against the virulence associated protein A (VapA), a major component of R. equi, to find the sequence for the needed antibody (mAb).
- This sequence was in vitro transcribed into mRNA, which could then express the full-length, VapA-specific mAbs.
- When directly delivered to the lungs of foals via nebulization, these mRNA-encoded mAbs stimulated the production of mAb inside the lungs for up to five days, offering passive immunity to the disease.
Implications
- The findings suggest a new, promising method to protect foals from R. equi pneumonia without the high costs and potential drawbacks of plasma transfusion.
- Beyond horses, this method could potentially offer an alternative for immunotherapeutic and immunoprophylactic applications for other species and diseases as well.
- This study constitutes a proof-of-concept for delivering nebulized mRNA monoclonal antibodies for intrapulmonary antibody expression in neonates.
Cite This Article
APA
Legere RM, Ott JA, Poveda C, Vanover D, Borba KER, Yeon Joo J, Martin CL, da Silveira BP, Bray JM, Landrock K, Wright GA, Blazier JC, Hillhouse AE, Benham-Duret AL, Mistretta B, Klein RL, Thompson SM, Woolums AR, Criscitiello MF, Berghman LR, Bordin AI, Santangelo PJ, Pollet J, Cohen ND.
(2025).
Nebulization of an mRNA-encoded monoclonal antibody for passive immunization of foals against Rhodococcus equi.
Mol Ther.
https://doi.org/10.1016/j.ymthe.2025.06.025 Publication
Researcher Affiliations
- Department of Large Animal Clinical Sciences, College of Veterinary Medicine & Biomedical Sciences, Texas A&M University, College Station, TX 77843, USA.
- Department of Veterinary Pathobiology, College of Veterinary Medicine & Biomedical Sciences, Texas A&M University, College Station, TX 77843, USA.
- National School of Tropical Medicine, Department of Pediatrics, Baylor College of Medicine, Houston, TX 77030, USA; Texas Children's Hospital Center for Vaccine Development, Baylor College of Medicine, Houston, TX 77030, USA.
- Wallace H. Coulter Department of Biomedical Engineering, Emory University & Georgia Institute of Technology, Atlanta, GA 30322, USA.
- Department of Large Animal Clinical Sciences, College of Veterinary Medicine & Biomedical Sciences, Texas A&M University, College Station, TX 77843, USA.
- Wallace H. Coulter Department of Biomedical Engineering, Emory University & Georgia Institute of Technology, Atlanta, GA 30322, USA.
- Department of Poultry Science, College of Agriculture & Life Sciences, Texas A&M University, College Station, TX 77843, USA.
- Department of Large Animal Clinical Sciences, College of Veterinary Medicine & Biomedical Sciences, Texas A&M University, College Station, TX 77843, USA.
- Department of Large Animal Clinical Sciences, College of Veterinary Medicine & Biomedical Sciences, Texas A&M University, College Station, TX 77843, USA.
- Department of Large Animal Clinical Sciences, College of Veterinary Medicine & Biomedical Sciences, Texas A&M University, College Station, TX 77843, USA.
- Department of Veterinary Pathobiology, College of Veterinary Medicine & Biomedical Sciences, Texas A&M University, College Station, TX 77843, USA.
- Texas A&M Institute for Genome Sciences and Society, Texas A&M University, College Station, TX 77843, USA.
- Texas A&M Institute for Genome Sciences and Society, Texas A&M University, College Station, TX 77843, USA.
- 10x Genomics, Inc., Pleasanton, CA 94588, USA.
- 10x Genomics, Inc., Pleasanton, CA 94588, USA.
- Department of Large Animal Clinical Sciences, College of Veterinary Medicine & Biomedical Sciences, Texas A&M University, College Station, TX 77843, USA.
- Mg Biologics, Inc., Ames, IA 50014, USA.
- Department of Pathobiology and Population Medicine, College of Veterinary Medicine, Mississippi State University, Mississippi State, MS 39762, USA.
- Department of Veterinary Pathobiology, College of Veterinary Medicine & Biomedical Sciences, Texas A&M University, College Station, TX 77843, USA.
- Department of Veterinary Pathobiology, College of Veterinary Medicine & Biomedical Sciences, Texas A&M University, College Station, TX 77843, USA; Department of Poultry Science, College of Agriculture & Life Sciences, Texas A&M University, College Station, TX 77843, USA.
- Department of Large Animal Clinical Sciences, College of Veterinary Medicine & Biomedical Sciences, Texas A&M University, College Station, TX 77843, USA.
- Wallace H. Coulter Department of Biomedical Engineering, Emory University & Georgia Institute of Technology, Atlanta, GA 30322, USA.
- National School of Tropical Medicine, Department of Pediatrics, Baylor College of Medicine, Houston, TX 77030, USA; Texas Children's Hospital Center for Vaccine Development, Baylor College of Medicine, Houston, TX 77030, USA.
- Department of Large Animal Clinical Sciences, College of Veterinary Medicine & Biomedical Sciences, Texas A&M University, College Station, TX 77843, USA. Electronic address: ncohen@tamu.edu.
Conflict of Interest Statement
Declaration of interests D.V. and P.J.S. have a patent application filed regarding the polymer used in this work. D.V. and P.J.S. are co-founders of Tether Therapeutics. The terms of these arrangements have been reviewed and approved by Emory University in accordance with its conflict-of-interest policies.
Citations
This article has been cited 0 times.Use Nutrition Calculator
Check if your horse's diet meets their nutrition requirements with our easy-to-use tool Check your horse's diet with our easy-to-use tool
Talk to a Nutritionist
Discuss your horse's feeding plan with our experts over a free phone consultation Discuss your horse's diet over a phone consultation
Submit Diet Evaluation
Get a customized feeding plan for your horse formulated by our equine nutritionists Get a custom feeding plan formulated by our nutritionists
