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Immune stealth-driven O2 serotype prevalence and potential for therapeutic antibodies against multidrug resistant Klebsiella pneumoniae

Pennini, Meghan E. ; De Marco, Anna ; Pelletier, Mark ; Bonnell, Jessica ; Cvitkovic, Romana ; Beltramello, Martina ; Cameroni, Elisabetta ; Bianchi, Siro ; Zatta, Fabrizia ; Zhao, Wei ; Xiao, Xiaodong ; Camara, Maria M. ; DiGiandomenico, Antonio ; Semenova, Elena ; Lanzavecchia, Antonio ; Warrener, Paul ; Suzich, JoAnn ; Wang, Qun ; Corti, Davide ; Stover, C. Kendall

In: Nature communications, 2017, vol. 8, p. 1991

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... More

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    Title
    • Immune stealth-driven O2 serotype prevalence and potential for therapeutic antibodies against multidrug resistant Klebsiella pneumoniae
    Author
    • 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
    Document Type
    • Postprint
    Publication Date
    • 2017-12-08
    Classification
    • Health
    OAI-PMH Identifier
    • oai:doc.rero.ch:20190926103804-ZE
    Submission No.
    • 20190926103804-ZE
    Summary
    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.