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Clinical and Vaccine Immunology, July 2007, p. 821-829, Vol. 14, No. 7
1071-412X/07/$08.00+0     doi:10.1128/CVI.00074-07
Copyright © 2007, American Society for Microbiology. All Rights Reserved.

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

Jeroen Geurtsen,^1,2 H. Alexander Banus,^3,4 Eric R. Gremmer,⁴ Henke Ferguson,⁴ Liset J. J. de la Fonteyne-Blankestijn,⁴ Jolanda P. Vermeulen,⁴ Jan A. M. A. Dormans,⁴ Jan Tommassen,¹ Peter van der Ley,² Frits R. Mooi,³ and Rob J. Vandebriel^4*

Department of Molecular Microbiology, Utrecht University, 3584 CH Utrecht, The Netherlands,¹ Vaccine Institute, 3720 AL Bilthoven, The Netherlands,² Laboratory for Vaccine-Preventable Diseases, National Institute of Public Health and the Environment, 3720 BA Bilthoven, The Netherlands,³ Laboratory of Toxicology, Pathology, and Genetics, National Institute of Public Health and the Environment, 3720 BA Bilthoven, The Netherlands⁴

Received 31 January 2007/ Returned for modification 7 March 2007/ Accepted 27 April 2007

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.

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* Corresponding author. Mailing address: Laboratory for Toxicology, Pathology and Genetics, National Institute of Public Health and the Environment, P.O. Box 1, 3720 BA Bilthoven, The Netherlands. Phone: 31-30-2742610. Fax: 31-30-2744446. E-mail: r.vandebriel{at}rivm.nl

Published ahead of print on 9 May 2007.

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Clinical and Vaccine Immunology, July 2007, p. 821-829, Vol. 14, No. 7
1071-412X/07/$08.00+0     doi:10.1128/CVI.00074-07
Copyright © 2007, American Society for Microbiology. All Rights Reserved.