ArticleThe Journal of infectious diseases2025
Epitope Conservation of AZD5148, a Broadly Neutralizing Anti-Toxin B Monoclonal Antibody, Among Diverse and Global Contemporary Clostridioides difficile Isolates.
Article in The Journal of infectious diseases, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.
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Who cites it
3 citing papers in PubMed.
- Monoclonal Antibodies Targeting Bacterial Infections: A Broad Review of the Field.BioDrugs : clinical immunotherapeutics, biopharmaceuticals and gene therapy · 2026Review
- Pooled analyses of Clostridioides difficile vaccine trials identify baseline predictors for vaccine response.Scientific reports · 2026Article
- The monoclonal antibody AZD5148 confers broad protection against TcdB-diverse Clostridioides difficile strains in mice.PLoS pathogens · 2025Article
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Authors and funding
12 authors.
Funding
Abstract
backgroundClostridioides difficile toxin B is a virulence factor for C. difficile infections and a clinically validated target for prevention of C. difficile infection recurrence. AZD5148 is a toxin B-neutralizing human monoclonal antibody that binds to an epitope on the toxin B glucosyltransferase domain. Herein, we aim to evaluate the conservation of this binding epitope using a collection of 9134 global C. difficile genomes obtained from a public repository to confirm that residues that are crucial for neutralization are conserved.
methodsUsing isolates collected between 2015 and 2023 from 2 independent sources, we performed variant calling, sequence typing, and phylogenetic analysis. We tested in vitro neutralization of cytotoxicity by AZD5148 using 2 cell lines.
resultsHerein, we showed that the AZD5148 epitope is highly conserved across all geographic regions and sequence types and has a higher average conservation frequency in its binding site (99.58%) when compared with bezlotoxumab (82.47%). AZD5148 also exhibited broad neutralization in vitro against 8 recently circulating ribotypes.
conclusionsOur comprehensive analysis of global sequences found the AZD5148 epitope to be highly conserved and thus unlikely to be affected by most genotypic variations in recently circulating C. difficile ribotypes and sequence types.
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