title: Microstructured liposome subunit vaccines reduce lung inflammation and bacterial load after Mycobacterium tuberculosis infection.
abstract: BACKGROUND
  Tuberculosis is a disease affecting millions of people throughout the world. One of the main problems in controlling the disease is the low efficacy of the Bacillus Calmette-Guérin (BCG) vaccine in protecting young adults. The development of new vaccines that induce a long-lasting immune response or that stimulate the immunity induced by BCG may improve the control of tuberculosis.
  
  
  METHODS
  The use of microstructured liposomes containing HspX, with or without MPL or CpG DNA adjuvants, as vaccines for tuberculosis was evaluated. The HspX-specific humoral and cellular immune responses to the different vaccine formulations were compared.
  
  
  RESULTS
  All vaccines containing liposome microparticles and HspX were immunogenic. Vaccines formulated with CpG DNA and HspX induced the strongest humoral and cellular immune responses, mainly by inducing interferon-γ and tumor necrosis factor-α expression by both CD4(+) and CD8(+) T cells. HspX and MPL mainly induced CD8(+) T-cell activation and specific humoral responses. When evaluated the protective efficacy of the formulations against Mycobacterium tuberculosis challenge, the microstructured liposome containing L-HspX and L-HspX-CPG DNA reduced both lung inflammatory lesions and the bacterial load.
  
  
  CONCLUSIONS
  We have thus demonstrated, for the first time, the use of microstructured liposomes as an adjuvant and delivery system for a vaccine formulation against tuberculosis.
authors.affiliation: Laboratório de Imunopatologia das Doenças Infecciosas, Instituto de Patologia Tropical e Saúde Pública, Universidade Federal de Goiás, Brazil.
authors.forename: Monalisa Martins
authors.initials: MM
authors.lastname: Trentini
authors.affiliation: Laboratório de Bacteriologia Molecular, Instituto de Patologia Tropical e Saúde Pública, Universidade Federal de Goiás, Brazil.
authors.forename: Fábio Muniz
authors.initials: FM
authors.lastname: de Oliveira
authors.affiliation: Laboratório de Nanotecnologia Farmacêutica - FarmaTec, Faculdade de Farmácia, Universidade Federal de Goiás, Brazil.
authors.forename: Marilisa Pedroso Nogueira
authors.initials: MP
authors.lastname: Gaeti
authors.affiliation: Laboratório de Patologia, Faculdade de Odontologia, Universidade Federal de Goiás, Brazil.
authors.forename: Aline Carvalho
authors.initials: AC
authors.lastname: Batista
authors.affiliation: Laboratório de Nanotecnologia Farmacêutica - FarmaTec, Faculdade de Farmácia, Universidade Federal de Goiás, Brazil.
authors.forename: Eliana Martins
authors.initials: EM
authors.lastname: Lima
authors.affiliation: Laboratório de Bacteriologia Molecular, Instituto de Patologia Tropical e Saúde Pública, Universidade Federal de Goiás, Brazil.
authors.forename: André
authors.initials: A
authors.lastname: Kipnis
authors.affiliation: Laboratório de Imunopatologia das Doenças Infecciosas, Instituto de Patologia Tropical e Saúde Pública, Universidade Federal de Goiás, Brazil. Electronic address: apkipnis@gmail.com.
authors.forename: Ana Paula
authors.initials: AP
authors.lastname: Junqueira-Kipnis
mesh_terms: D000276:Adjuvants, Immunologic / Q000494:pharmacology; D000818:Animals; D000907:Antibodies, Bacterial / Q000276:immunology; D000942:Antigens, Bacterial / Q000276:immunology*; D058491:Bacterial Load; D001426:Bacterial Proteins / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D018899:CpG Islands; D005260:Female; D056724:Immunity, Humoral; D007074:Immunoglobulin G / Q000276:immunology; D007249:Inflammation / Q000276:immunology; D007371:Interferon-gamma / Q000276:immunology; D008081:Liposomes / Q000276:immunology*; D008168:Lung / Q000382:microbiology / Q000473:pathology; D008213:Lymphocyte Activation; D008807:Mice, Inbred BALB C; D009169:Mycobacterium tuberculosis; D014376:Tuberculosis / Q000517:prevention & control*; D032581:Tuberculosis Vaccines / Q000276:immunology*; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology; D022223:Vaccines, Subunit / Q000276:immunology
chemical_list: D000276:Adjuvants, Immunologic; D000907:Antibodies, Bacterial; D000942:Antigens, Bacterial; D001426:Bacterial Proteins; C118127:HspX protein, Mycobacterium tuberculosis; D007074:Immunoglobulin G; D008081:Liposomes; D032581:Tuberculosis Vaccines; D014409:Tumor Necrosis Factor-alpha; D022223:Vaccines, Subunit; D007371:Interferon-gamma
keywords: Adjuvants; HspX; Latent antigens; Liposome; Tuberculosis; Vaccine