Location: Foodborne Toxin Detection and Prevention Research
Title: A novel Shiga toxin 2a neutralizing antibody therapeutic with low immunogenicity and high efficacyA novel Shiga toxin 2a neutralizing antibody therapeutic with low immunogenicity and high efficacyAuthor
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KIRKLAND, MARINA - Orise Fellow |
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PATFIELD, STEPHANIE - Former ARS Employee |
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HUGHES, ANNA - Former ARS Employee |
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Hernlem, Bradley - Brad |
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He, Xiaohua |
Submitted to: Antimicrobial Agents and Chemotherapy
Publication Type: Peer Reviewed Journal Publication Acceptance Date: 10/18/2023 Publication Date: 12/4/2023 Citation: Kirkland, M., Patfield, S., Hughes, A.C., Hernlem, B.J., He, X. 2023. A novel Shiga toxin 2a neutralizing antibody therapeutic with low immunogenicity and high efficacyA novel Shiga toxin 2a neutralizing antibody therapeutic with low immunogenicity and high efficacy. Antimicrobial Agents and Chemotherapy. 68(1). https://doi.org/10.1128/aac.00598-23. DOI: https://doi.org/10.1128/aac.00598-23 Interpretive Summary: This paper entails research and development of a novel humanized monoclonal antibody, Hu-mAb 2-5, with therapeutic potential against Shiga toxin 2a (Stx2a). Evidence is provided to support the antibody’s potential to mitigate tissue damage that may lead to hemolytic uremia syndrome (HUS), a complication of Shiga toxin producing Escherichia coli (STEC) infection. The results obtained from this study are significant because the use of antibiotics in STEC infections is controversial due to the risk of antibiotic-induced stress upregulating the production of toxin in E. coli. Current treatment remains supportive and there are no specific therapies. Therefore, passive application of Stx-neutralizing antibodies is an important and viable therapeutic option to prevent the development and progression of HUS. Technical Abstract: Shiga toxin producing Escherichia coli infections are difficult to treat due to the risk of antibiotic-induced stress upregulating the production of toxin, medical treatment is consequently limited to supportive care to prevent the development of hemolytic uremia syndrome (HUS). Here, we introduce a humanized mouse monoclonal antibody (Hu-mAb 2-5) targeting Stx2a, the most common Shiga toxin subtype identified from outbreaks. We demonstrate that Hu-mAb 2-5 has low immunogenicity ex vivo and high neutralizing efficacy in vivo, protecting mice from mortality and HUS related tissue damage. |