title: Protective efficacy of different strategies employing Mycobacterium leprae heat-shock protein 65 against tuberculosis.
abstract: BACKGROUND
  Tuberculosis is a major threat to human health. The high disease burden remains unaffected and the appearance of extremely drug-resistant strains in different parts of the world argues in favor of the urgent need for a new effective vaccine. One of the promising candidates is heat-shock protein 65 when used as a genetic vaccine (DNAhsp65). Nonetheless, there are substantial data indicating that BCG, the only available anti-TB vaccine for clinical use, provides other important beneficial effects in immunized infants.
  
  
  METHODS
  We compared the protective efficacy of BCG and Hsp65 antigens in mice using different strategies: i) BCG, single dose subcutaneously; ii) naked DNAhsp65, four doses, intramuscularly; iii) liposomes containing DNAhsp65, single dose, intranasally; iv) microspheres containing DNAhsp65 or rHsp65, single dose, intramuscularly; and v) prime-boost with subcutaneous BCG and intramuscular DNAhsp65.
  
  
  RESULTS
  All the immunization protocols were able to protect mice against infection, with special benefits provided by DNAhsp65 in liposomes and prime-boost strategies.
  
  
  CONCLUSIONS
  Among the immunization protocols tested, liposomes containing DNAhsp65 represent the most promising strategy for the development of a new anti-TB vaccine.
authors.affiliation: Universidade de São Paulo, Núcleo de Pesquisas em Tuberculose, Departamento de Bioquímica e Imunologia, Faculdade de Medicina de Ribeirão Preto, FMRP-USP, 14049-900 Ribeirão Preto, SP, Brasil.
authors.forename: Patrícia R M
authors.initials: PR
authors.lastname: Souza
authors.forename: Carlos R
authors.initials: CR
authors.lastname: Zárate-Bladés
authors.forename: Juliana I
authors.initials: JI
authors.lastname: Hori
authors.forename: Simone G
authors.initials: SG
authors.lastname: Ramos
authors.forename: Deison S
authors.initials: DS
authors.lastname: Lima
authors.forename: Tatiana
authors.initials: T
authors.lastname: Schneider
authors.forename: Rogério S
authors.initials: RS
authors.lastname: Rosada
authors.forename: Lucimara G L
authors.initials: LG
authors.lastname: Torre
authors.forename: Maria Helena A
authors.initials: MH
authors.lastname: Santana
authors.forename: Izaíra T
authors.initials: IT
authors.lastname: Brandão
authors.forename: Ana P
authors.initials: AP
authors.lastname: Masson
authors.forename: Arlete A M
authors.initials: AA
authors.lastname: Coelho-Castelo
authors.forename: Vânia L
authors.initials: VL
authors.lastname: Bonato
authors.forename: Fabio C S
authors.initials: FC
authors.lastname: Galetti
authors.forename: Eduardo D
authors.initials: ED
authors.lastname: Gonçalves
authors.forename: Domingos A
authors.initials: DA
authors.lastname: Botte
authors.forename: Jeanne B M
authors.initials: JB
authors.lastname: Machado
authors.forename: Celio L
authors.initials: CL
authors.lastname: Silva
mesh_terms: D000818:Animals; D001426:Bacterial Proteins / Q000276:immunology* / Q000378:metabolism; D001428:Bacterial Vaccines / Q000008:administration & dosage / Q000276:immunology*; D018834:Chaperonin 60; D018833:Chaperonins / Q000276:immunology* / Q000378:metabolism; D004269:DNA, Bacterial / Q000235:genetics; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D051379:Mice; D008807:Mice, Inbred BALB C; D009166:Mycobacterium leprae / Q000235:genetics / Q000378:metabolism*; D010957:Plasmids; D014376:Tuberculosis / Q000517:prevention & control*
chemical_list: D001426:Bacterial Proteins; D001428:Bacterial Vaccines; D018834:Chaperonin 60; D004269:DNA, Bacterial; C074119:heat-shock protein 65, Mycobacterium; D018833:Chaperonins