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

Meghan E. Pennini, Anna Marco, Mark Pelletier, Jessica Bonnell, Romana Cvitkovic, Martina Beltramello, Elisabetta Cameroni, Siro Bianchi, Fabrizia Zatta, Wei Zhao, Xiaodong Xiao, Maria M. Camara, Antonio DiGiandomenico, Elena Semenova, Antonio Lanzavecchia, Paul Warrener, JoAnn Suzich, Qun Wang (), Davide Corti () and C. Kendall Stover ()
Additional contact information
Meghan E. Pennini: MedImmune
Anna Marco: Humabs BioMed SA, a subsidiary of Vir Biotechnology, Inc.
Mark Pelletier: MedImmune
Jessica Bonnell: MedImmune
Romana Cvitkovic: MedImmune
Martina Beltramello: Humabs BioMed SA, a subsidiary of Vir Biotechnology, Inc.
Elisabetta Cameroni: Humabs BioMed SA, a subsidiary of Vir Biotechnology, Inc.
Siro Bianchi: Humabs BioMed SA, a subsidiary of Vir Biotechnology, Inc.
Fabrizia Zatta: Humabs BioMed SA, a subsidiary of Vir Biotechnology, Inc.
Wei Zhao: MedImmune
Xiaodong Xiao: MedImmune
Maria M. Camara: MedImmune
Antonio DiGiandomenico: MedImmune
Elena Semenova: MedImmune
Antonio Lanzavecchia: Institute for Research in Biomedicine, Università della Svizzera Italliana
Paul Warrener: MedImmune
JoAnn Suzich: MedImmune
Qun Wang: MedImmune
Davide Corti: Humabs BioMed SA, a subsidiary of Vir Biotechnology, Inc.
C. Kendall Stover: MedImmune

Nature Communications, 2017, vol. 8, issue 1, 1-12

Abstract: Abstract 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.

Date: 2017
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DOI: 10.1038/s41467-017-02223-7

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