title: Boosting BCG with inert spores improves immunogenicity and induces specific IL-17 responses in a murine model of bovine tuberculosis.
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.
authors.affiliation: Vaccine Immunology Team, Department of Bacteriology, Animal & Plant Health Agency (APHA), Addlestone, Surrey KT15 3NB, UK.
authors.forename: M Carmen
authors.initials: MC
authors.lastname: Garcia-Pelayo
authors.affiliation: Vaccine Immunology Team, Department of Bacteriology, Animal & Plant Health Agency (APHA), Addlestone, Surrey KT15 3NB, UK. Electronic address: daryan.kaveh@apha.gsi.gov.uk.
authors.forename: Daryan A
authors.initials: DA
authors.lastname: Kaveh
authors.affiliation: School of Biological Sciences, Royal Holloway, University of London, Egham, Surrey TW20 0EX, UK.
authors.forename: Laura
authors.initials: L
authors.lastname: Sibly
authors.affiliation: Vaccine Immunology Team, Department of Bacteriology, Animal & Plant Health Agency (APHA), Addlestone, Surrey KT15 3NB, UK.
authors.forename: Paul R
authors.initials: PR
authors.lastname: Webb
authors.affiliation: Vaccine Immunology Team, Department of Bacteriology, Animal & Plant Health Agency (APHA), Addlestone, Surrey KT15 3NB, UK.
authors.forename: Naomi C
authors.initials: NC
authors.lastname: Bull
authors.affiliation: School of Biological Sciences, Royal Holloway, University of London, Egham, Surrey TW20 0EX, UK.
authors.forename: Simon M
authors.initials: SM
authors.lastname: Cutting
authors.affiliation: Vaccine Immunology Team, Department of Bacteriology, Animal & Plant Health Agency (APHA), Addlestone, Surrey KT15 3NB, UK.
authors.forename: Philip J
authors.initials: PJ
authors.lastname: Hogarth
mesh_terms: D000818:Animals; D001500:BCG Vaccine / Q000008:administration & dosage / Q000276:immunology*; D001412:Bacillus subtilis / Q000276:immunology*; D002417:Cattle; D002478:Cells, Cultured; D004195:Disease Models, Animal; D005260:Female; D007117:Immunization, Secondary; D000071497:Immunogenicity, Vaccine; D007279:Injections, Subcutaneous; D007371:Interferon-gamma / Q000276:immunology / Q000378:metabolism; D020381:Interleukin-17 / Q000276:immunology* / Q000378:metabolism; D007376:Interleukin-2 / Q000276:immunology / Q000378:metabolism; D008807:Mice, Inbred BALB C; D013154:Spleen / Q000276:immunology* / Q000378:metabolism; D013171:Spores, Bacterial / Q000276:immunology*; D018417:Th1 Cells / Q000276:immunology / Q000378:metabolism; D058504:Th17 Cells / Q000276:immunology / Q000378:metabolism; D018418:Th2 Cells / Q000276:immunology / Q000378:metabolism; D013997:Time Factors; D014380:Tuberculosis, Bovine / Q000276:immunology / Q000378:metabolism / Q000382:microbiology / Q000517:prevention & control*; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology / Q000378:metabolism
chemical_list: D001500:BCG Vaccine; C000611649:IFNG protein, mouse; D020381:Interleukin-17; D007376:Interleukin-2; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma
keywords: BCG; Bovine tuberculosis; Heterologous prime-boost; Spores; Vaccine