Lung pathology and immediate hypersensitivity in a mouse model after vaccination with pertussis vaccines and challenge with Bordetella pertussis

Vaccine. 2007 Mar 8;25(12):2346-60. doi: 10.1016/j.vaccine.2005.09.062. Epub 2006 Dec 12.

Abstract

While evaluating vaccine efficacy against clinical Bordetella pertussis isolates in mice, after challenge vaccinated mice showed increased lung pathology with eosinophilia, compared to challenged, non-vaccinated animals. This led us to study bacterial clearance, lung pathology, lung TNF-alpha expression, and parameters of immediate hypersensitivity (IH), being serum IgE levels, eosinophil numbers in the bronchoalveolar lavage fluid, and ex vivo IL-4, IL-5, IL-10, IL-13, and IFN-gamma production by the bronchial lymph node cells. BALB/c mice received a combined Diphtheria (D), Tetanus (T), Poliomyelitis, and whole-cell Pertussis vaccine (WCV), a combined D, T, and three-component acellular Pertussis vaccine (ACV), aluminium hydroxide adjuvant, or PBS, 28 and 14 days before B. pertussis infection. Similarly treated non-infected mice were taken as a control. Infection induced pathology; this induction was stronger after (especially WCV) vaccination. WCV but not ACV vaccination induced TNF-alpha expression after challenge. After challenge, IH parameters were strongly increased by (especially ACV) vaccination. Vaccinated IL-4 KO mice showed similar clearance and pathology, in the absence of IgE and with reduced numbers of eosinophils. Vaccinated (Th1-deficient) T-bet KO mice showed reduced clearance and similar pathology. In summary, after challenge vaccination increased lung pathology, TNF-alpha expression (only WCV), and IH parameters. Th1 cells were critical for clearance.

MeSH terms

  • Administration, Intranasal
  • Animals
  • Bordetella pertussis / growth & development
  • Bordetella pertussis / immunology*
  • Diphtheria-Tetanus-Pertussis Vaccine / administration & dosage
  • Diphtheria-Tetanus-Pertussis Vaccine / immunology
  • Diphtheria-Tetanus-Pertussis Vaccine / toxicity
  • Female
  • Hypersensitivity, Immediate / chemically induced*
  • Hypersensitivity, Immediate / metabolism
  • Immunoglobulin E / blood
  • Interferon-gamma / metabolism
  • Interleukin-10 / metabolism
  • Interleukin-13 / metabolism
  • Interleukin-4 / genetics
  • Interleukin-4 / metabolism
  • Interleukin-5 / metabolism
  • Lung / immunology
  • Lung / microbiology
  • Lung / pathology*
  • Lymph Nodes / immunology
  • Lymph Nodes / metabolism
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • Mice, Inbred Strains
  • Mice, Knockout
  • Pertussis Vaccine / administration & dosage
  • Pertussis Vaccine / immunology*
  • Pertussis Vaccine / toxicity
  • Tumor Necrosis Factor-alpha / metabolism
  • Vaccines, Acellular / administration & dosage
  • Vaccines, Acellular / immunology
  • Vaccines, Acellular / toxicity
  • Whooping Cough / immunology*
  • Whooping Cough / prevention & control

Substances

  • Diphtheria-Tetanus-Pertussis Vaccine
  • Interleukin-13
  • Interleukin-5
  • Pertussis Vaccine
  • Tumor Necrosis Factor-alpha
  • Vaccines, Acellular
  • Interleukin-10
  • Interleukin-4
  • Immunoglobulin E
  • Interferon-gamma