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
Show more…
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
-
-
Classification
-
Medicine
-
License
-
License undefined
-
Identifiers
-
-
Persistent URL
-
https://n2t.net/ark:/12658/srd1318967
Statistics
Document views: 64
File downloads: