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. 2025 Sep 3;33(9):4175-4192.
doi: 10.1016/j.ymthe.2025.06.025. Epub 2025 Jun 14.

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

Rebecca M Legere  1 , Jeannine A Ott  2 , Cristina Poveda  3 , Daryll Vanover  4 , Karin E R Borba  1 , Jae Yeon Joo  4 , Cameron L Martin  5 , Bibiana P da Silveira  1 , Jocelyne M Bray  1 , Kerstin Landrock  1 , Gus A Wright  2 , J Chistensen Blazier  6 , Andrew E Hillhouse  6 , Ashley L Benham-Duret  7 , Brandon Mistretta  7 , Rafaela L Klein  1 , Sarah M Thompson  8 , Amelia R Woolums  9 , Michael F Criscitiello  2 , Luc R Berghman  10 , Angela I Bordin  1 , Philip J Santangelo  4 , Jeroen Pollet  3 , Noah D Cohen  11
Affiliations

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

Rebecca M Legere et al. Mol Ther. .

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.

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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.

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