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

IF 12.1 1区医学 Q1 BIOTECHNOLOGY & APPLIED MICROBIOLOGY

Molecular Therapy Pub Date : 2025-06-14 DOI:10.1016/j.ymthe.2025.06.025

Rebecca M Legere,Jeannine A Ott,Cristina Poveda,Daryll Vanover,Karin E R Borba,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,Phillip J Santangelo,Jeroen Pollet,Noah D Cohen

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引用次数: 0

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 IgG1 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.

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一种mrna编码单克隆抗体雾化用于马驹被动免疫马红球菌。

吸入马红球菌可在世界各地的人和动物中引起严重的肺炎，最常影响马驹。预防马驹马雷氏肺炎的标准是输血高免疫血浆，这是昂贵的，并且有不良反应的风险。我们的目标是通过将编码抗毒力相关蛋白A （VapA）的马单克隆抗体（mAb）的mRNA直接雾化到肺部来被动免疫马驹。来自免疫马的vapa特异性记忆b细胞用于鉴定和选择马IgG1单抗的序列。体外转录编码该序列的mRNA，在体外表达全长、vapa特异性单克隆抗体，并在雾化后至少5天内安全有效地在马驹体内产生肺内单克隆抗体。这些发现为产生用于马免疫治疗和免疫预防的mrna编码单克隆抗体建立了平台，并证明了在新生儿肺内表达雾化mRNA-mAb的可行性。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Molecular Therapy 医学-生物工程与应用微生物

CiteScore

19.20

自引率

3.20%

发文量

357

审稿时长

3 months

期刊介绍： Molecular Therapy is the leading journal for research in gene transfer, vector development, stem cell manipulation, and therapeutic interventions. It covers a broad spectrum of topics including genetic and acquired disease correction, vaccine development, pre-clinical validation, safety/efficacy studies, and clinical trials. With a focus on advancing genetics, medicine, and biotechnology, Molecular Therapy publishes peer-reviewed research, reviews, and commentaries to showcase the latest advancements in the field. With an impressive impact factor of 12.4 in 2022, it continues to attract top-tier contributions.