Protective efficacy of different strategies employing Mycobacterium leprae heat-shock protein 65 against tuberculosis.
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.
Souza
Patrícia R M
PR
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.
Zárate-Bladés
Carlos R
CR
Hori
Juliana I
JI
Ramos
Simone G
SG
Lima
Deison S
DS
Schneider
Tatiana
T
Rosada
Rogério S
RS
Torre
Lucimara G L
LG
Santana
Maria Helena A
MH
Brandão
Izaíra T
IT
Masson
Ana P
AP
Coelho-Castelo
Arlete A M
AA
Bonato
Vânia L
VL
Galetti
Fabio C S
FC
Gonçalves
Eduardo D
ED
Botte
Domingos A
DA
Machado
Jeanne B M
JB
Silva
Celio L
CL
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*
D001426:Bacterial Proteins; D001428:Bacterial Vaccines; D018834:Chaperonin 60; D004269:DNA, Bacterial; C074119:heat-shock protein 65, Mycobacterium; D018833:Chaperonins