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Immunogenicity and safety of a tetravalent E. coli O-antigen bioconjugate vaccine in animal models

2016; Elsevier BV; Volume: 34; Issue: 35 Linguagem: Inglês

10.1016/j.vaccine.2016.06.067

1873-2518

Germie P. J. M. van den Dobbelsteen, Kellen C. Faé, Jan Serroyen, Ingrid M. van den Nieuwenhof, Martin Braun, Micha A. Haeuptle, Dominique Sirena, J Schneider, Cristina Alaimo, Gerd Lipowsky, Veronica Gambillara-Fonck, Michael Wacker, Jan Poolman,

Viral gastroenteritis research and epidemiology

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 (2 μg or 20 μg per O-antigen, subcutaneously), mice (0.2 μg or 2 μg per O-antigen, subcutaneously) and rats (0.4 μg or 4 μg per O-antigen, intramuscularly). Antibody persistence and boostability were evaluated in rats using O6-EPA monovalent conjugate (0.4 μg O-antigen/dose, intramuscularly). Toxicity was assessed in rats (16 μg 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 168 days 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.