title: Immunogenicity and safety of a tetravalent E. coli O-antigen bioconjugate vaccine in animal models.
abstract: Extra-intestinal pathogenic Escherichia coli (ExPEC) are major human pathogens; however, no protective vaccine is currently available. We assessed in animal models the immunogenicity and safety of a 4-valent E. coli conjugate vaccine (ExPEC-4V, serotypes O1, O2, O6 and O25 conjugated to Exotoxin A from Pseudomonas aeruginosa (EPA)) produced using a novel in vivo bioconjugation method.
  
  
  
  Three doses of ExPEC-4V (with or without aluminum hydroxide) were administered to rabbits (2μg or 20μg per O-antigen, subcutaneously), mice (0.2μg or 2μg per O-antigen, subcutaneously) and rats (0.4μg or 4μg per O-antigen, intramuscularly). Antibody persistence and boostability were evaluated in rats using O6-EPA monovalent conjugate (0.4μg O-antigen/dose, intramuscularly). Toxicity was assessed in rats (16μg total polysaccharide, intramuscularly). Serum IgG and IgM antibodies were measured by ELISA.
  
  
  
  Robust antigen-specific IgG responses were observed in all animal models, with increased responses in rabbits when administered with adjuvant. O antigen-specific antibody responses persisted up to 168days post-priming. Booster immunization induced a rapid recall response. Toxicity of ExPEC-4V when administered to rats was considered to be at the no observed adverse effect level.
  
  
  
  ExPEC-4V conjugate vaccine showed good immunogenicity and tolerability in animal models supporting progression to clinical evaluation.
authors.affiliation: Bacterial Vaccines Discovery & Early Development, Janssen Vaccines and Prevention B.V. (former Crucell Holland B.V.), Part of the Janssen Pharmaceutical Companies of Johnson and Johnson, Archimedesweg 4-6, 2333CN Leiden, The Netherlands. Electronic address: gdobbel@its.jnj.com.
authors.forename: Germie P J M
authors.initials: GPJM
authors.lastname: van den Dobbelsteen
authors.affiliation: Bacterial Vaccines Discovery & Early Development, Janssen Vaccines and Prevention B.V. (former Crucell Holland B.V.), Part of the Janssen Pharmaceutical Companies of Johnson and Johnson, Archimedesweg 4-6, 2333CN Leiden, The Netherlands. Electronic address: kfae@its.jnj.com.
authors.forename: Kellen C
authors.initials: KC
authors.lastname: Faé
authors.affiliation: Bacterial Vaccines Discovery & Early Development, Janssen Vaccines and Prevention B.V. (former Crucell Holland B.V.), Part of the Janssen Pharmaceutical Companies of Johnson and Johnson, Archimedesweg 4-6, 2333CN Leiden, The Netherlands. Electronic address: jserroy1@its.jnj.com.
authors.forename: Jan
authors.initials: J
authors.lastname: Serroyen
authors.affiliation: Bacterial Vaccines Discovery & Early Development, Janssen Vaccines and Prevention B.V. (former Crucell Holland B.V.), Part of the Janssen Pharmaceutical Companies of Johnson and Johnson, Archimedesweg 4-6, 2333CN Leiden, The Netherlands. Electronic address: Ivanden@its.jnj.com.
authors.forename: Ingrid M
authors.initials: IM
authors.lastname: van den Nieuwenhof
authors.affiliation: LimmaTech Biologics (former GlycoVaxyn AG), Grabenstrasse 3, 8952 Schlieren, Switzerland. Electronic address: Martin.Braun@lmtbio.com.
authors.forename: Martin
authors.initials: M
authors.lastname: Braun
authors.affiliation: LimmaTech Biologics (former GlycoVaxyn AG), Grabenstrasse 3, 8952 Schlieren, Switzerland; Current address: Molecular Partners AG, Wagistrasse 14, 8952 Zürich-Schlieren, Switzerland. Electronic address: Micha.Haeuptle@molecularpartners.com.
authors.forename: Micha A
authors.initials: MA
authors.lastname: Haeuptle
authors.affiliation: LimmaTech Biologics (former GlycoVaxyn AG), Grabenstrasse 3, 8952 Schlieren, Switzerland. Electronic address: Dominique.Sirena@lmtbio.com.
authors.forename: Dominique
authors.initials: D
authors.lastname: Sirena
authors.affiliation: LimmaTech Biologics (former GlycoVaxyn AG), Grabenstrasse 3, 8952 Schlieren, Switzerland. Electronic address: Joerg.Schneider@lmtbio.com.
authors.forename: Joerg
authors.initials: J
authors.lastname: Schneider
authors.affiliation: LimmaTech Biologics (former GlycoVaxyn AG), Grabenstrasse 3, 8952 Schlieren, Switzerland. Electronic address: Cristina.Alaimo@lmtbio.com.
authors.forename: Cristina
authors.initials: C
authors.lastname: Alaimo
authors.affiliation: LimmaTech Biologics (former GlycoVaxyn AG), Grabenstrasse 3, 8952 Schlieren, Switzerland. Electronic address: Gerd.Lipowsky@lmtbio.com.
authors.forename: Gerd
authors.initials: G
authors.lastname: Lipowsky
authors.affiliation: LimmaTech Biologics (former GlycoVaxyn AG), Grabenstrasse 3, 8952 Schlieren, Switzerland. Electronic address: Veronica.Gambillara@lmtbio.com.
authors.forename: Veronica
authors.initials: V
authors.lastname: Gambillara-Fonck
authors.affiliation: LimmaTech Biologics (former GlycoVaxyn AG), Grabenstrasse 3, 8952 Schlieren, Switzerland; Current address: Wacker Biotech Consulting, Obere Hönggerstrasse 9a, 8103 Unterengstringen, Switzerland. Electronic address: Michael.Wacker@wbioc.com.
authors.forename: Michael
authors.initials: M
authors.lastname: Wacker
authors.affiliation: Bacterial Vaccines Discovery & Early Development, Janssen Vaccines and Prevention B.V. (former Crucell Holland B.V.), Part of the Janssen Pharmaceutical Companies of Johnson and Johnson, Archimedesweg 4-6, 2333CN Leiden, The Netherlands. Electronic address: JPoolman@its.jnj.com.
authors.forename: Jan T
authors.initials: JT
authors.lastname: Poolman
mesh_terms: D036002:ADP Ribose Transferases / Q000276:immunology; D000276:Adjuvants, Immunologic / Q000008:administration & dosage; D000818:Animals; D000907:Antibodies, Bacterial / Q000097:blood; D001427:Bacterial Toxins / Q000276:immunology; D004926:Escherichia coli; D004927:Escherichia coli Infections / Q000517:prevention & control*; D022361:Escherichia coli Vaccines / Q000276:immunology*; D005098:Exotoxins / Q000276:immunology; D005260:Female; D007117:Immunization, Secondary; D000071497:Immunogenicity, Vaccine; D051379:Mice; D008813:Mice, Inbred ICR; D019055:No-Observed-Adverse-Effect Level; D019081:O Antigens / Q000276:immunology*; D011817:Rabbits; D051381:Rats; D017207:Rats, Sprague-Dawley; D018675:Toxicity Tests; D018074:Vaccines, Conjugate / Q000276:immunology; D037521:Virulence Factors / Q000276:immunology; D000097668:Pseudomonas aeruginosa Exotoxin A
chemical_list: D036002:ADP Ribose Transferases; D000276:Adjuvants, Immunologic; D000907:Antibodies, Bacterial; D001427:Bacterial Toxins; D022361:Escherichia coli Vaccines; D005098:Exotoxins; D019081:O Antigens; D018074:Vaccines, Conjugate; D037521:Virulence Factors; D000097668:Pseudomonas aeruginosa Exotoxin A
keywords: Conjugate vaccine; Escherichia coli; Extra-intestinal pathogenic E. coli (ExPEC); Immunogenicity; Safety; Vaccine