title: Bactericidal monoclonal antibodies specific to the lipopolysaccharide O antigen from multidrug-resistant Escherichia coli clone ST131-O25b:H4 elicit protection in mice.
abstract: The Escherichia coli sequence type 131 (ST131)-O25b:H4 clone has spread worldwide and become responsible for a significant proportion of multidrug-resistant extraintestinal infections. We generated humanized monoclonal antibodies (MAbs) that target the lipopolysaccharide O25b antigen conserved within this lineage. These MAbs bound to the surface of live bacterial cells irrespective of the capsular type expressed. In a serum bactericidal assay in vitro, MAbs induced >95% bacterial killing in the presence of human serum as the complement source. Protective efficacy at low antibody doses was observed in a murine model of bacteremia. The mode of action in vivo was investigated by using aglycosylated derivatives of the protective MAbs. The significant binding to live E. coli cells and the in vitro and in vivo efficacy were corroborated in assays using bacteria grown in human serum to mimic relevant clinical conditions. Given the dry pipeline of novel antibiotics against multidrug-resistant Gram-negative pathogens, passive immunization with bactericidal antibodies offers a therapeutic alternative to control infections caused by E. coli ST131-O25b:H4.
authors.affiliation: Arsanis Biosciences GmbH, Vienna, Austria.
authors.forename: Valéria
authors.initials: V
authors.lastname: Szijártó
authors.affiliation: Arsanis Biosciences GmbH, Vienna, Austria.
authors.forename: Luis M
authors.initials: LM
authors.lastname: Guachalla
authors.affiliation: Arsanis Biosciences GmbH, Vienna, Austria.
authors.forename: Zehra C
authors.initials: ZC
authors.lastname: Visram
authors.affiliation: Arsanis Biosciences GmbH, Vienna, Austria.
authors.forename: Katharina
authors.initials: K
authors.lastname: Hartl
authors.affiliation: Arsanis Biosciences GmbH, Vienna, Austria.
authors.forename: Cecília
authors.initials: C
authors.lastname: Varga
authors.affiliation: Arsanis Biosciences GmbH, Vienna, Austria.
authors.forename: Irina
authors.initials: I
authors.lastname: Mirkina
authors.affiliation: Arsanis Biosciences GmbH, Vienna, Austria.
authors.forename: Jakub
authors.initials: J
authors.lastname: Zmajkovic
authors.affiliation: Arsanis Biosciences GmbH, Vienna, Austria.
authors.forename: Adriana
authors.initials: A
authors.lastname: Badarau
authors.affiliation: Arsanis Biosciences GmbH, Vienna, Austria.
authors.forename: Gerhild
authors.initials: G
authors.lastname: Zauner
authors.affiliation: Arsanis Biosciences GmbH, Vienna, Austria.
authors.forename: Clara
authors.initials: C
authors.lastname: Pleban
authors.affiliation: Arsanis Biosciences GmbH, Vienna, Austria.
authors.forename: Zoltán
authors.initials: Z
authors.lastname: Magyarics
authors.affiliation: Arsanis Biosciences GmbH, Vienna, Austria.
authors.forename: Eszter
authors.initials: E
authors.lastname: Nagy
authors.affiliation: Arsanis Biosciences GmbH, Vienna, Austria gabor.nagy@arsanis.com.
authors.forename: Gábor
authors.initials: G
authors.lastname: Nagy
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology* / Q000627:therapeutic use*; D000911:Antibodies, Monoclonal / Q000494:pharmacology* / Q000627:therapeutic use*; D024901:Drug Resistance, Multiple, Bacterial; D004926:Escherichia coli / Q000187:drug effects* / Q000378:metabolism*; D004927:Escherichia coli Infections / Q000188:drug therapy / Q000382:microbiology; D005260:Female; D051379:Mice; D019081:O Antigens / Q000378:metabolism*
chemical_list: D000900:Anti-Bacterial Agents; D000911:Antibodies, Monoclonal; D019081:O Antigens