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VACCINE RESEARCH

Lipopolysaccharide Analogs Improve Efficacy of Acellular Pertussis Vaccine and Reduce Type I Hypersensitivity in Mice

Jeroen Geurtsen, H. Alexander Banus, Eric R. Gremmer, Henke Ferguson, Liset J. J. de la Fonteyne-Blankestijn, Jolanda P. Vermeulen, Jan A. M. A. Dormans, Jan Tommassen, Peter van der Ley, Frits R. Mooi, Rob J. Vandebriel
Jeroen Geurtsen
1Department of Molecular Microbiology, Utrecht University, 3584 CH Utrecht, The Netherlands
2Vaccine Institute, 3720 AL Bilthoven, The Netherlands
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H. Alexander Banus
3Laboratory for Vaccine-Preventable Diseases, National Institute of Public Health and the Environment, 3720 BA Bilthoven, The Netherlands
4Laboratory of Toxicology, Pathology, and Genetics, National Institute of Public Health and the Environment, 3720 BA Bilthoven, The Netherlands
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Eric R. Gremmer
4Laboratory of Toxicology, Pathology, and Genetics, National Institute of Public Health and the Environment, 3720 BA Bilthoven, The Netherlands
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Henke Ferguson
4Laboratory of Toxicology, Pathology, and Genetics, National Institute of Public Health and the Environment, 3720 BA Bilthoven, The Netherlands
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Liset J. J. de la Fonteyne-Blankestijn
4Laboratory of Toxicology, Pathology, and Genetics, National Institute of Public Health and the Environment, 3720 BA Bilthoven, The Netherlands
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Jolanda P. Vermeulen
4Laboratory of Toxicology, Pathology, and Genetics, National Institute of Public Health and the Environment, 3720 BA Bilthoven, The Netherlands
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Jan A. M. A. Dormans
4Laboratory of Toxicology, Pathology, and Genetics, National Institute of Public Health and the Environment, 3720 BA Bilthoven, The Netherlands
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Jan Tommassen
1Department of Molecular Microbiology, Utrecht University, 3584 CH Utrecht, The Netherlands
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Peter van der Ley
2Vaccine Institute, 3720 AL Bilthoven, The Netherlands
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Frits R. Mooi
3Laboratory for Vaccine-Preventable Diseases, National Institute of Public Health and the Environment, 3720 BA Bilthoven, The Netherlands
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Rob J. Vandebriel
4Laboratory of Toxicology, Pathology, and Genetics, National Institute of Public Health and the Environment, 3720 BA Bilthoven, The Netherlands
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  • For correspondence: r.vandebriel@rivm.nl
DOI: 10.1128/CVI.00074-07
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ABSTRACT

Pertussis is an infectious disease of the respiratory tract that is caused by the gram-negative bacterium Bordetella pertussis. Although acellular pertussis (aP) vaccines are safe, they are not fully effective and thus require improvement. In contrast to whole-cell pertussis (wP) vaccines, aP vaccines do not contain lipopolysaccharide (LPS). Monophosphoryl lipid A (MPL) and Neisseria meningitidis LpxL2 LPS have been shown to display immune-stimulating activity while exerting little endotoxin activity. Therefore, we evaluated whether these LPS analogs could increase the efficacy of the aP vaccine. Mice were vaccinated with diphtheria-tetanus-aP vaccine with aluminum, MPL, or LpxL2 LPS adjuvant before intranasal challenge with B. pertussis. Compared to vaccination with the aluminum adjuvant, vaccination with either LPS analog resulted in lower colonization and a higher pertussis toxin-specific serum immunoglobulin G level, indicating increased efficacy. Vaccination with either LPS analog resulted in reduced lung eosinophilia, reduced eosinophil numbers in the bronchoalveolar lavage fluid, and the ex vivo production of interleukin-4 (IL-4) by bronchial lymph node cells and IL-5 by spleen cells, suggesting reduced type I hypersensitivity. Vaccination with either LPS analog increased serum IL-6 levels, although these levels remained well below the level induced by wP, suggesting that supplementation with LPS analogs may induce some reactogenicity but reactogenicity considerably less than that induced by the wP vaccine. In conclusion, these results indicate that supplementation with LPS analogs forms a promising strategy that can be used to improve aP vaccines.

  • Copyright © 2007 American Society for Microbiology
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Lipopolysaccharide Analogs Improve Efficacy of Acellular Pertussis Vaccine and Reduce Type I Hypersensitivity in Mice
Jeroen Geurtsen, H. Alexander Banus, Eric R. Gremmer, Henke Ferguson, Liset J. J. de la Fonteyne-Blankestijn, Jolanda P. Vermeulen, Jan A. M. A. Dormans, Jan Tommassen, Peter van der Ley, Frits R. Mooi, Rob J. Vandebriel
Clinical and Vaccine Immunology Jul 2007, 14 (7) 821-829; DOI: 10.1128/CVI.00074-07

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Lipopolysaccharide Analogs Improve Efficacy of Acellular Pertussis Vaccine and Reduce Type I Hypersensitivity in Mice
Jeroen Geurtsen, H. Alexander Banus, Eric R. Gremmer, Henke Ferguson, Liset J. J. de la Fonteyne-Blankestijn, Jolanda P. Vermeulen, Jan A. M. A. Dormans, Jan Tommassen, Peter van der Ley, Frits R. Mooi, Rob J. Vandebriel
Clinical and Vaccine Immunology Jul 2007, 14 (7) 821-829; DOI: 10.1128/CVI.00074-07
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KEYWORDS

Bordetella pertussis
Diphtheria-Tetanus-acellular Pertussis Vaccines
Hypersensitivity, Immediate
Lipopolysaccharides
Vaccines, Acellular
Whooping Cough

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