Nebulization of an mRNA-Encoded Monoclonal Antibody for Passive Immunization of Foals Against Rhodococcus equi

Authors

• Rebecca M Legere
• Jeannine A Ott
• Cristina Poveda
• Daryll Vanover
• Karin E R Borba
• Jae Yeon Joo
• Cameron L Martin
• Bibiana P da Silveira
• Jocelyne M Bray
• Kerstin Landrock
• Gus A Wright
• J Chistensen Blazier
• Andrew E Hillhouse
• Ashley L Benham-Duret
• Brandon Mistretta
• Rafaela L Klein
• Sarah M Thompson
• Amelia R Woolums
• Michael F Criscitiello
• Luc R Berghman
• Angela I Bordin
• Philip J Santangelo
• Jeroen Pollet
• Noah D Cohen

Language

English

Publication Date

9-3-2025

Journal

Molecular Therapy

DOI

10.1016/j.ymthe.2025.06.025

PMID

40518672

PMCID

PMC12432880

PubMedCentral® Posted Date

6-14-2025

PubMedCentral® Full Text Version

Post-print

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.

Keywords

Animals, Rhodococcus equi, Horses, Antibodies, Monoclonal, RNA, Messenger, Immunization, Passive, Actinomycetales Infections, Bacterial Proteins, Horse Diseases, Nebulizers and Vaporizers, foal, immunity, aerosol, mRNA, monoclonal antibody, Rhodococcus equi, nebulization, transfection, poly-beta-amino-thio-ester

Published Open-Access

yes

Recommended Citation

Legere, Rebecca M; Ott, Jeannine A; Poveda, Cristina; et al., "Nebulization of an mRNA-Encoded Monoclonal Antibody for Passive Immunization of Foals Against Rhodococcus equi" (2025). Faculty, Staff and Students Publications. 7896.
https://digitalcommons.library.tmc.edu/baylor_docs/7896