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Vaccine. 2016 Jul 29;34(35):4152-4160. doi: 10.1016/j.vaccine.2016.06.067. Epub 2016 Jul 6.

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

Author information

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.

KEYWORDS:

Conjugate vaccine; Escherichia coli; Extra-intestinal pathogenic E. coli (ExPEC); Immunogenicity; Safety; Vaccine

PMID:
27395567
DOI:
10.1016/j.vaccine.2016.06.067
[Indexed for MEDLINE]

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