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Tuberculosis (Edinb) ; 98: 97-103, 2016 05.
Article in English | MEDLINE | ID: mdl-27156624

ABSTRACT

Tuberculosis (TB) remains a global pandemic, in both animals and man, and novel vaccines are urgently required. Heterologous prime-boost of BCG represents a promising strategy for improved TB vaccines, with respiratory delivery the most efficacious to date. Such an approach may be an ideal vaccination strategy against bovine TB (bTB), but respiratory vaccination presents a technical challenge in cattle. Inert bacterial spores represent an attractive vaccine vehicle. Therefore we evaluated whether parenterally administered spores are efficacious when used as a BCG boost in a murine model of immunity against Mycobacterium bovis. Here we report the use of heat-killed, TB10.4 adsorbed, Bacillus subtilis spores delivered via subcutaneous injection to boost immunity primed by BCG. We demonstrate that this approach improves the immunogenicity of BCG. Interestingly, this associated with substantial boosting of IL-17 responses; considered to be important in protective immunity against TB. These data demonstrate that parenteral delivery of spores represents a promising vaccine vehicle for boosting BCG, and identifies potential for optimisation for use as a vaccine for bovine TB.


Subject(s)
BCG Vaccine/immunology , Bacillus subtilis/immunology , Immunogenicity, Vaccine , Interleukin-17/immunology , Spleen/immunology , Spores, Bacterial/immunology , Tuberculosis, Bovine/prevention & control , Animals , BCG Vaccine/administration & dosage , Cattle , Cells, Cultured , Disease Models, Animal , Female , Immunization, Secondary , Injections, Subcutaneous , Interferon-gamma/immunology , Interferon-gamma/metabolism , Interleukin-17/metabolism , Interleukin-2/immunology , Interleukin-2/metabolism , Mice, Inbred BALB C , Spleen/metabolism , Th1 Cells/immunology , Th1 Cells/metabolism , Th17 Cells/immunology , Th17 Cells/metabolism , Th2 Cells/immunology , Th2 Cells/metabolism , Time Factors , Tuberculosis, Bovine/immunology , Tuberculosis, Bovine/metabolism , Tuberculosis, Bovine/microbiology , Tumor Necrosis Factor-alpha/immunology , Tumor Necrosis Factor-alpha/metabolism
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