Germie P J M van den Dobbelsteen1, Kellen C Faé2, Jan Serroyen3, Ingrid M van den Nieuwenhof4, Martin Braun5, Micha A Haeuptle6, Dominique Sirena7, Joerg Schneider8, Cristina Alaimo9, Gerd Lipowsky10, Veronica Gambillara-Fonck11, Michael Wacker12, Jan T Poolman13. 1. 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. 2. 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. 3. 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. 4. 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. 5. LimmaTech Biologics (former GlycoVaxyn AG), Grabenstrasse 3, 8952 Schlieren, Switzerland. Electronic address: Martin.Braun@lmtbio.com. 6. 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. 7. LimmaTech Biologics (former GlycoVaxyn AG), Grabenstrasse 3, 8952 Schlieren, Switzerland. Electronic address: Dominique.Sirena@lmtbio.com. 8. LimmaTech Biologics (former GlycoVaxyn AG), Grabenstrasse 3, 8952 Schlieren, Switzerland. Electronic address: Joerg.Schneider@lmtbio.com. 9. LimmaTech Biologics (former GlycoVaxyn AG), Grabenstrasse 3, 8952 Schlieren, Switzerland. Electronic address: Cristina.Alaimo@lmtbio.com. 10. LimmaTech Biologics (former GlycoVaxyn AG), Grabenstrasse 3, 8952 Schlieren, Switzerland. Electronic address: Gerd.Lipowsky@lmtbio.com. 11. LimmaTech Biologics (former GlycoVaxyn AG), Grabenstrasse 3, 8952 Schlieren, Switzerland. Electronic address: Veronica.Gambillara@lmtbio.com. 12. 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. 13. 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.
Abstract
BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: ExPEC-4V conjugate vaccine showed good immunogenicity and tolerability in animal models supporting progression to clinical evaluation.
BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: ExPEC-4V conjugate vaccine showed good immunogenicity and tolerability in animal models supporting progression to clinical evaluation.
Authors: Darren Abbanat; Todd A Davies; Karen Amsler; Wenping He; Kellen Fae; Sarah Janssen; Jan T Poolman; Germie P J M van den Dobbelsteen Journal: Clin Vaccine Immunol Date: 2017-12-05
Authors: Neil Ravenscroft; Martin Braun; Joerg Schneider; Anita M Dreyer; Michael Wetter; Micha A Haeuptle; Stefan Kemmler; Michael Steffen; Dominique Sirena; Stefan Herwig; Paula Carranza; Claire Jones; Andrew J Pollard; Michael Wacker; Michael Kowarik Journal: Glycobiology Date: 2019-08-20 Impact factor: 4.313
Authors: Jeremy A Duke; Amy V Paschall; Lloyd S Robinson; Cory J Knoot; Evgeny Vinogradov; Nichollas E Scott; Mario F Feldman; Fikri Y Avci; Christian M Harding Journal: ACS Infect Dis Date: 2021-10-11 Impact factor: 5.084