Lung pathology and immediate hypersensitivity in a mouse model after vaccination with pertussis vaccines and challenge with Bordetella pertussis.
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.
Vandebriel
Rob J
RJ
Laboratory for Toxicology, Pathology and Genetics, National Institute of Public Health and the Environment, 3720 BA Bilthoven, The Netherlands. r.vandebriel@rivm.nl
Gremmer
Eric R
ER
Vermeulen
Jolanda P
JP
Hellwig
Sandra M M
SM
Dormans
Jan A M A
JA
Roholl
Paul J M
PJ
Mooi
Frits R
FR
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
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