title: Lung pathology and immediate hypersensitivity in a mouse model after vaccination with pertussis vaccines and challenge with Bordetella pertussis.
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.
authors.affiliation: Laboratory for Toxicology, Pathology and Genetics, National Institute of Public Health and the Environment, 3720 BA Bilthoven, The Netherlands. r.vandebriel@rivm.nl
authors.forename: Rob J
authors.initials: RJ
authors.lastname: Vandebriel
authors.forename: Eric R
authors.initials: ER
authors.lastname: Gremmer
authors.forename: Jolanda P
authors.initials: JP
authors.lastname: Vermeulen
authors.forename: Sandra M M
authors.initials: SM
authors.lastname: Hellwig
authors.forename: Jan A M A
authors.initials: JA
authors.lastname: Dormans
authors.forename: Paul J M
authors.initials: PJ
authors.lastname: Roholl
authors.forename: Frits R
authors.initials: FR
authors.lastname: Mooi
mesh_terms: D000281:Administration, Intranasal; D000818:Animals; D001886:Bordetella pertussis / Q000254:growth & development / Q000276:immunology*; D015721:Diphtheria-Tetanus-Pertussis Vaccine / Q000008:administration & dosage / Q000276:immunology / Q000633:toxicity; D005260:Female; D006969:Hypersensitivity, Immediate / Q000139:chemically induced* / Q000378:metabolism; D007073:Immunoglobulin E / Q000097:blood; D007371:Interferon-gamma / Q000378:metabolism; D016753:Interleukin-10 / Q000378:metabolism; D018793:Interleukin-13 / Q000378:metabolism; D015847:Interleukin-4 / Q000235:genetics / Q000378:metabolism; D015848:Interleukin-5 / Q000378:metabolism; D008168:Lung / Q000276:immunology / Q000382:microbiology / Q000473:pathology*; D008198:Lymph Nodes / Q000276:immunology / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008815:Mice, Inbred Strains; D018345:Mice, Knockout; D010567:Pertussis Vaccine / Q000008:administration & dosage / Q000276:immunology* / Q000633:toxicity; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D022282:Vaccines, Acellular / Q000008:administration & dosage / Q000276:immunology / Q000633:toxicity; D014917:Whooping Cough / Q000276:immunology* / Q000517:prevention & control
chemical_list: D015721:Diphtheria-Tetanus-Pertussis Vaccine; D018793:Interleukin-13; D015848:Interleukin-5; D010567:Pertussis Vaccine; D014409:Tumor Necrosis Factor-alpha; D022282:Vaccines, Acellular; D016753:Interleukin-10; D015847:Interleukin-4; D007073:Immunoglobulin E; D007371:Interferon-gamma