Protective efficacy of different strategies employing Mycobacterium leprae heat-shock protein 65 against tuberculosis

Expert Opin Biol Ther. 2008 Sep;8(9):1255-64. doi: 10.1517/14712598.8.9.1255.

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.

Conclusion: Among the immunization protocols tested, liposomes containing DNAhsp65 represent the most promising strategy for the development of a new anti-TB vaccine.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Bacterial Proteins / immunology*
  • Bacterial Proteins / metabolism
  • Bacterial Vaccines / administration & dosage
  • Bacterial Vaccines / immunology*
  • Chaperonin 60
  • Chaperonins / immunology*
  • Chaperonins / metabolism
  • DNA, Bacterial / genetics
  • Enzyme-Linked Immunosorbent Assay
  • Female
  • Mice
  • Mice, Inbred BALB C
  • Mycobacterium leprae / genetics
  • Mycobacterium leprae / metabolism*
  • Plasmids
  • Tuberculosis / prevention & control*

Substances

  • Bacterial Proteins
  • Bacterial Vaccines
  • Chaperonin 60
  • DNA, Bacterial
  • heat-shock protein 65, Mycobacterium
  • Chaperonins