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- Title
Exploiting human immune repertoire transgenic mice for protective monoclonal antibodies against antimicrobial resistant Acinetobacter baumannii.
- Authors
Baker, Stephen; Krishna, Aishwarya; Higham, Sophie; Naydenova, Plamena; O'Leary, Siobhan; Scott, Josefin Bartholdson; Harcourt, Katherine; Forrest, Sally; Goulding, David; Thi Nguyen, To Nguyen; Toan, Nguyen Duc; Alekseeva, Elizaveta; Zhou, Qingqing; Andreozzi, Ilaria; Sobotic, Barbara; Craig, Hannah; Wong, Vivian; Forrest-Owen, Nichola; Sanchez, Dana Moreno; Pearce, Claire
- Abstract
The use of monoclonal antibodies for the control of drug resistant nosocomial bacteria may alleviate a reliance on broad spectrum antimicrobials for treatment of infection. We identify monoclonal antibodies that may prevent infection caused by carbapenem resistant Acinetobacter baumannii. We use human immune repertoire mice (Kymouse platform mice) as a surrogate for human B cell interrogation to establish an unbiased strategy to probe the antibody-accessible target landscape of clinically relevant A. baumannii. After immunisation of the Kymouse platform mice with A. baumannii derived outer membrane vesicles (OMV) we identify 297 antibodies and analyse 26 of these for functional potential. These antibodies target lipooligosaccharide (OCL1), the Oxa-23 protein, and the KL49 capsular polysaccharide. We identify a single monoclonal antibody (mAb1416) recognising KL49 capsular polysaccharide to demonstrate prophylactic in vivo protection against a carbapenem resistant A. baumannii lineage associated with neonatal sepsis mortality in Asia. Our end-to-end approach identifies functional monoclonal antibodies with prophylactic potential against major lineages of drug resistant bacteria accounting for phylogenetic diversity and clinical relevance without existing knowledge of a specific target antigen. Such an approach might be scaled for a additional clinically important bacterial pathogens in the post-antimicrobial era. In this work, the authors describe immunisation of human antibody immune repertoire transgenic mice as a surrogate to define protective human antibody reactivity to clinically diverse, antibiotic resistant Acinetobacter baumannii.
- Subjects
EXTRACELLULAR vesicles; ACINETOBACTER baumannii; TRANSGENIC mice; NEONATAL sepsis; POLYSACCHARIDES
- Publication
Nature Communications, 2024, Vol 15, Issue 1, p1
- ISSN
2041-1723
- Publication type
Article
- DOI
10.1038/s41467-024-52357-8