Molecular therapy : the journal of the American Society of Gene Therapy · 2025
Nebulization of an mRNA-encoded monoclonal antibody for passive immunization of foals against Rhodococcus equi.
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Legere Rebecca M, Ott Jeannine A, Poveda Cristina, Vanover Daryll, Borba Karin E R, Yeon Joo Jae, Martin Cameron L, da Silveira Bibiana P, Bray Jocelyne M, Landrock Kerstin, Wright Gus A, Blazier J Chistensen, Hillhouse Andrew E, Benham-Duret Ashley L, Mistretta Brandon, Klein Rafaela L, Thompson Sarah M, Woolums Amelia R, Criscitiello Michael F, Berghman Luc R, Bordin Angela I, Santangelo Philip J, Pollet Jeroen, Cohen Noah D
Аннотация
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.