Nebulization of an mRNA-encoded monoclonal antibody for passive immunization of foals against Rhodococcus equi

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

doi:10.1016/j.ymthe.2025.06.025

Nebulization of an mRNA-encoded monoclonal antibody for passive immunization of foals against Rhodococcus equi

Mol Ther. 2025 Jun 14:S1525-0016(25)00476-9. doi: 10.1016/j.ymthe.2025.06.025. Online ahead of print.

Authors

Rebecca M Legere¹, Jeannine A Ott², Cristina Poveda³, Daryll Vanover⁴, Karin E R Borba¹, Jae Yeon Joo⁴, Cameron L Martin⁵, Bibiana P da Silveira¹, Jocelyne M Bray¹, Kerstin Landrock¹, Gus A Wright², J Chistensen Blazier⁶, Andrew E Hillhouse⁶, Ashley L Benham-Duret⁷, Brandon Mistretta⁷, Rafaela L Klein¹, Sarah M Thompson⁸, Amelia R Woolums⁹, Michael F Criscitiello², Luc R Berghman¹⁰, Angela I Bordin¹, Philip J Santangelo⁴, Jeroen Pollet³, Noah D Cohen¹¹

Affiliations

¹ Department of Large Animal Clinical Sciences, College of Veterinary Medicine & Biomedical Sciences, Texas A&M University, College Station, TX 77843, USA.
² Department of Veterinary Pathobiology, College of Veterinary Medicine & Biomedical Sciences, Texas A&M University, College Station, TX 77843, USA.
³ 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.
⁴ Wallace H. Coulter Department of Biomedical Engineering, Emory University & Georgia Institute of Technology, Atlanta, GA 30322, USA.
⁵ Department of Poultry Science, College of Agriculture & Life Sciences, Texas A&M University, College Station, TX 77843, USA.
⁶ Texas A&M Institute for Genome Sciences and Society, Texas A&M University, College Station, TX 77843, USA.
⁷ 10x Genomics, Inc., Pleasanton, CA 94588, USA.
⁸ Mg Biologics, Inc., Ames, IA 50014, USA.
⁹ Department of Pathobiology and Population Medicine, College of Veterinary Medicine, Mississippi State University, Mississippi State, MS 39762, USA.
¹⁰ 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.
¹¹ 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.

PMID: 40518672
DOI: 10.1016/j.ymthe.2025.06.025

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: Rhodococcus equi; aerosol; foal; immunity; mRNA; monoclonal antibody; nebulization; poly-beta-amino-thio-ester; transfection.