title: Mycobacterium tuberculosis culture filtrate proteins plus CpG Oligodeoxynucleotides confer protection to Mycobacterium bovis BCG-primed mice by inhibiting interleukin-4 secretion.
abstract: Culture filtrate proteins (CFP) are potential targets for tuberculosis vaccine development. We previously showed that despite the high level of gamma interferon (IFN-gamma) production elicited by homologous immunization with CFP plus CpG oligodeoxynucleotides (CFP/CpG), we did not observe protection when these mice were challenged with Mycobacterium tuberculosis. In order to use the IFN-gamma-inducing ability of CFP antigens, in this study we evaluated a prime-boost heterologous immunization based on CFP/CpG to boost Mycobacterium bovis BCG vaccination in order to find an immunization schedule that could induce protection. Heterologous BCG-CFP/CpG immunization provided significant protection against experimental tuberculosis, and this protection was sustained during the late phase of infection and was even better than that conferred by a single BCG immunization. The protection was associated with high levels of antigen-specific IFN-gamma and interleukin-17 (IL-17) and low IL-4 production. The deleterious role of IL-4 was confirmed when IL-4 knockout mice vaccinated with CFP/CpG showed consistent protection similar to that elicited by BCG-CFP/CpG heterologous immunization. These findings show that a single dose of CFP/CpG can represent a new strategy to boost the protection conferred by BCG vaccination. Moreover, different immunological parameters, such as IFN-gamma and IL-17 and tightly regulated IL-4 secretion, seem to contribute to the efficacy of this tuberculosis vaccine.
authors.affiliation: Núcleo de Pesquisas em Tuberculose, Departamento de Bioquímica e Imunologia, Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, SP, Brazil.
authors.forename: Denise Morais
authors.initials: DM
authors.lastname: da Fonseca
authors.forename: Celio Lopes
authors.initials: CL
authors.lastname: Silva
authors.forename: Pryscilla Fanini
authors.initials: PF
authors.lastname: Wowk
authors.forename: Marina Oliveira E
authors.initials: MO
authors.lastname: Paula
authors.forename: Simone Gusmão
authors.initials: SG
authors.lastname: Ramos
authors.forename: Cynthia
authors.initials: C
authors.lastname: Horn
authors.forename: Gilles
authors.initials: G
authors.lastname: Marchal
authors.forename: Vânia Luiza Deperon
authors.initials: VL
authors.lastname: Bonato
mesh_terms: D000276:Adjuvants, Immunologic / Q000008:administration & dosage; D000818:Animals; D001426:Bacterial Proteins / Q000276:immunology*; D015169:Colony Count, Microbial; D005260:Female; D017353:Gene Deletion; D007117:Immunization, Secondary / Q000379:methods*; D007371:Interferon-gamma / Q000276:immunology; D020381:Interleukin-17 / Q000276:immunology; D015847:Interleukin-4 / Q000037:antagonists & inhibitors* / Q000172:deficiency / Q000378:metabolism; D008168:Lung / Q000276:immunology / Q000382:microbiology / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009163:Mycobacterium bovis / Q000276:immunology*; D009169:Mycobacterium tuberculosis / Q000276:immunology*; D009838:Oligodeoxyribonucleotides / Q000008:administration & dosage*; D014376:Tuberculosis / Q000517:prevention & control; D032581:Tuberculosis Vaccines / Q000276:immunology*
chemical_list: D000276:Adjuvants, Immunologic; D001426:Bacterial Proteins; C408982:CPG-oligonucleotide; D020381:Interleukin-17; D009838:Oligodeoxyribonucleotides; D032581:Tuberculosis Vaccines; D015847:Interleukin-4; D007371:Interferon-gamma