Journal article

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
  • English
Classification
Medicine
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https://susi.usi.ch/usi/documents/318967
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