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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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  • FIG. 1.
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    FIG. 1.

    Colonization of the lungs by B. pertussis. Mice were subcutaneously injected with (H) 1/5, (M) 1/25, or (L) 1/125 HD DTaP vaccine plus aluminum (alum) or MPL or (C) with the adjuvants only twice before intranasal B. pertussis infection. At 3 and 7 days after infection the lungs were excised and the number of viable B. pertussis organisms in the right lung lobes was determined. Each symbol represents the number of bacteria in the lung of an individual mouse; horizontal lines represent the group average. Nonboxed numbers show P values when the different vaccine doses were compared for the same adjuvant and day of killing. Boxed numbers show P values when the different adjuvants are compared for the same vaccine dose and day of killing. ANOVA was followed by t test. The results of a single representative experiment of three are shown.

  • FIG. 2.
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    FIG. 2.

    Ptx-specific IgG in serum. Mice were injected s.c. with 1/5 HD DTaP vaccine plus aluminum (alum) or MPL or with the adjuvants only twice before intranasal B. pertussis infection. At 3 and 7 days after infection, the mice were euthanized. Serum was taken, and serial dilutions of test and positive control sera were tested for Ptx-specific IgG. The data are indicated as the means ± standard errors of the means (n = 5). ANOVA was followed by t test. The results of a single representative experiment of two are shown.

  • FIG. 3.
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    FIG. 3.

    Lung eosinophilia. Mice were injected s.c. with 1/5 HD DTaP vaccine plus aluminum (alum) or MPL or with the adjuvants only twice before intranasal B. pertussis infection. At 3 days after infection, the left lung lobes were excised. Each symbol represents an individual mouse; horizontal lines represent the group average. The Mann-Whitney U test was used. The results of a single representative experiment of two are shown.

  • FIG. 4.
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    FIG. 4.

    Total serum IgE. Mice were injected s.c. with 1/5 HD DTaP vaccine plus aluminum (alum) or MPL or with the adjuvants only twice before intranasal B. pertussis infection. At 3 days after infection, serum was taken and assayed for total IgE. The data are indicated as the means ± standard errors of the means (n = 6). ANOVA was followed by use of the Bonferroni correction. The results of a single representative experiment of two are shown.

  • FIG. 5.
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    FIG. 5.

    (A) IL-4 production by ex vivo ConA-stimulated bronchial LN cells. Mice were injected s.c. with 1/5 HD DTaP vaccine plus aluminum (alum) or MPL or with the adjuvants only twice before intranasal B. pertussis infection. Three days after infection, the bronchial LNs were excised, the cells were cultured with ConA for 24 h, and the supernatants were analyzed for their cytokine contents. (B) IL-5 production by splenocytes stimulated ex vivo with heat-killed B. pertussis. The splenocytes were cultured with heat-killed B. pertussis for 72 h, and the supernatants were analyzed for their cytokine contents. The data are indicated as the means ± standard errors of the means (n = 6). ANOVA was followed by use of the Bonferroni correction. The results of a single representative experiment of two are shown.

  • FIG. 6.
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    FIG. 6.

    Colonization of the lungs by B. pertussis. Mice were injected s.c. with PBS or 1/10 HD DTaP vaccine plus aluminum, LpxL2 LPS, or MPL twice before intranasal B. pertussis infection. At 5 days after infection the lungs were excised, and the number of viable B. pertussis organisms was determined. Each symbol represents the number of bacteria in the lung of an individual mouse; horizontal lines represent the group average. ANOVA was followed by t test. The results of a single representative experiment of two are shown.

  • FIG. 7.
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    FIG. 7.

    BALF eosinophil numbers. Mice were injected s.c. with 1/10 HD DTaP vaccine plus aluminum, LpxL2 LPS, or MPL or with PBS twice before intranasal B. pertussis infection. At 5 days after infection, lung lavage was performed and the BALF cells were counted and visually differentiated. The data are indicated as the means ± standard errors of the means (n = 6). ANOVA was followed by use of the Bonferroni correction. The results of a single representative experiment of two are shown.

  • FIG. 8.
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    FIG. 8.

    Serum IL-6. Mice were injected s.c. with 1/10 HD wP vaccine; 1/10 HD DTaP vaccine plus aluminum, LpxL2 LPS, or MPL; or PBS. Serum IL-6 concentrations were determined 4 h postimmunization. The data are indicated as the means ± standard errors of the means (n = 7). ANOVA was followed by use of the Bonferroni correction. The results of a single representative experiment of two are shown.

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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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    • ABSTRACT
    • MATERIALS AND METHODS
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KEYWORDS

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

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