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ARS Home » Pacific West Area » Albany, California » Western Regional Research Center » Foodborne Toxin Detection and Prevention Research » Research » Publications at this Location » Publication #404837
Research Project: Technologies for the Detection of Bacterial and Plant Toxins and Allergens that Impact Food Safety and Food Defense

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 efficacy

Author
item KIRKLAND, MARINA - Orise Fellow
item PATFIELD, STEPHANIE - Former ARS Employee
item HUGHES, ANNA - Former ARS Employee
item Hernlem, Bradley - Brad
item 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.