Immune stealth-driven O2 serotype prevalence and potential for therapeutic antibodies against multidrug resistant Klebsiella pneumoniae
- Pennini, Meghan E. MedImmune, 1 Medimmune Way, Gaithersburg, MD 20878, USA
- De Marco, Anna Humabs BioMed SA, a subsidiary of Vir Biotechnology, Inc., Via Mirasole 1, 6500 Bellinzona, Switzerland
- Pelletier, Mark MedImmune, 1 Medimmune Way, Gaithersburg, MD 20878, USA
- Bonnell, Jessica MedImmune, 1 Medimmune Way, Gaithersburg, MD 20878, USA
- Cvitkovic, Romana MedImmune, 1 Medimmune Way, Gaithersburg, MD 20878, USA
- Beltramello, Martina Humabs BioMed SA, a subsidiary of Vir Biotechnology, Inc., Via Mirasole 1, 6500 Bellinzona, Switzerland
- Cameroni, Elisabetta Humabs BioMed SA, a subsidiary of Vir Biotechnology, Inc., Via Mirasole 1, 6500 Bellinzona, Switzerland
- Bianchi, Siro Humabs BioMed SA, a subsidiary of Vir Biotechnology, Inc., Via Mirasole 1, 6500 Bellinzona, Switzerland
- Zatta, Fabrizia Humabs BioMed SA, a subsidiary of Vir Biotechnology, Inc., Via Mirasole 1, 6500 Bellinzona, Switzerland
- Zhao, Wei MedImmune, 1 Medimmune Way, Gaithersburg, MD 20878, USA
- Xiao, Xiaodong MedImmune, 1 Medimmune Way, Gaithersburg, MD 20878, USA
- Camara, Maria M. MedImmune, 1 Medimmune Way, Gaithersburg, MD 20878, USA
- DiGiandomenico, Antonio MedImmune, 1 Medimmune Way, Gaithersburg, MD 20878, USA
- Semenova, Elena MedImmune, 1 Medimmune Way, Gaithersburg, MD 20878, USA
- Lanzavecchia, Antonio Institute for Research in Biomedicine (IRB), Faculty of Biomedical Sciences, Università della Svizzera italiana, Switzerland
- Warrener, Paul MedImmune, 1 Medimmune Way, Gaithersburg, MD 20878, USA
- Suzich, JoAnn MedImmune, 1 Medimmune Way, Gaithersburg, MD 20878, USA
- Wang, Qun MedImmune, 1 Medimmune Way, Gaithersburg, MD 20878, USA
- Corti, Davide Humabs BioMed SA, a subsidiary of Vir Biotechnology, Inc., Via Mirasole 1, 6500 Bellinzona, Switzerland
- Stover, C. Kendall MedImmune, 1 Medimmune Way, Gaithersburg, MD 20878, USA
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08.12.2017
Published in:
- Nature communications. - 2017, vol. 8, p. 1991
English
Emerging multidrug-resistant bacteria are a challenge for modern medicine, but how these pathogens are so successful is not fully understood. Robust antibacterial vaccines have prevented and reduced resistance suggesting a pivotal role for immunity in deterring antibiotic resistance. Here, we show the increased prevalence of Klebsiella pneumoniae lipopolysaccharide O2 serotype strains in all major drug resistance groups correlating with a paucity of anti-O2 antibodies in human B cell repertoires. We identify human monoclonal antibodies to O-antigens that are highly protective in mouse models of infection, even against heavily encapsulated strains. These antibodies, including a rare anti-O2 specific antibody, synergistically protect against drug-resistant strains in adjunctive therapy with meropenem, a standard-of-care antibiotic, confirming the importance of immune assistance in antibiotic therapy. These findings support an antibody-based immunotherapeutic strategy even for highly resistant K. pneumoniae infections, and underscore the effect humoral immunity has on evolving drug resistance.
- Language
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- English
- Classification
- Medicine
- License
- License undefined
- Identifiers
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- RERO DOC 327178
- DOI 10.1038/s41467-017-02223-7
- ARK ark:/12658/srd1318967
- Persistent URL
- https://n2t.net/ark:/12658/srd1318967
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