| 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; Roberts, Leah; Watson, Simon; Clare, Simon; Torok, Mili Estee; Dougan, Gordon; Kellam, Paul; Tregoning, John S; Reece, Stephen T |
| Publisher Information: |
Springer Nature; //doi.org/10.1038/s41467-024-52357-8 |
| Publication Year: |
2024 |
| Collection: |
Apollo - University of Cambridge Repository |
| Subject Terms: |
Acinetobacter baumannii; Animals; Humans; Antibodies; Monoclonal; Acinetobacter Infections; Mice; Transgenic; Anti-Bacterial Agents; Bacterial; Female; Carbapenems; Drug Resistance; Lipopolysaccharides |
| Description: |
Acknowledgements: This work was supported by grants from the Bill & Melinda Gates Foundation, OPP1159947 (P.K.) and INV-040928 (S.T.R.), the UK Medical Research Council Newton Fund (M.E.T.), the Viet Nam Ministry of Science and Technology (M.E.T.), and Wellcome Senior Research Fellowship 215515/Z/19/Z (S.B.). Additional support was provided by the Academy of Medical Sciences (M.E.T.), the Health Foundation (M.E.T.), and the National Institute for Health Research Cambridge Biomedical Research Centre (M.E.T. and G.D.). The funders did not play any role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript. ; Funder: Bill and Melinda Gates Foundation (Bill & Melinda Gates Foundation); doi: https://doi.org/10.13039/100000865 ; 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 ... |
| Document Type: |
article in journal/newspaper |
| File Description: |
application/pdf; application/zip; text/xml |
| Language: |
English |
| Relation: |
52357; https://www.repository.cam.ac.uk/handle/1810/373649 |
| Availability: |
https://www.repository.cam.ac.uk/handle/1810/373649 |
| Rights: |
Attribution-NonCommercial-NoDerivatives 4.0 International ; http://creativecommons.org/licenses/by-nc-nd/4.0/ |
| Accession Number: |
edsbas.6291CB85 |
| Database: |
BASE |