A Toll-like receptor-2-directed fusion protein vaccine against tuberculosis

Clin Vaccine Immunol. 2007 Jul;14(7):902-6. doi: 10.1128/CVI.00077-07.

Abstract

A fusion protein designated CSU-F36 was constructed that consisted of acylated Rv1411, a potent Toll-like receptor-2 agonist, fused to ESAT-6, a well-characterized immunogenic protein from Mycobacterium tuberculosis. The CSU-F36 fusion protein strongly induced interleukin 12 secretion from macrophages and induced the increased accumulation of CD4 T cells capable of secreting gamma interferon in the lungs of infected mice. These mice were significantly protected from low-dose aerosol challenge with M. tuberculosis, even with CSU-F36 delivered in a simple depot material. This "natural adjuvant"-containing system could potentially bypass the need for more expensive TH1-inducing adjuvants and could be applied to many mycobacterial proteins to provide effective and cheap new vaccines against tuberculosis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adjuvants, Immunologic / metabolism
  • Adjuvants, Immunologic / pharmacology
  • Animals
  • Antigens, Bacterial / genetics
  • Antigens, Bacterial / immunology
  • Antigens, Bacterial / metabolism
  • BCG Vaccine / immunology
  • BCG Vaccine / pharmacology
  • Interleukin-12 / immunology
  • Lung / immunology
  • Lung / pathology
  • Mice
  • Mice, Inbred C57BL
  • Mycobacterium tuberculosis / immunology*
  • Recombinant Fusion Proteins / genetics
  • Recombinant Fusion Proteins / immunology
  • Recombinant Fusion Proteins / metabolism
  • Toll-Like Receptor 2 / agonists
  • Toll-Like Receptor 2 / immunology*
  • Toll-Like Receptor 2 / metabolism
  • Tuberculosis, Pulmonary / immunology*
  • Tuberculosis, Pulmonary / pathology
  • Tuberculosis, Pulmonary / prevention & control*
  • Vaccines, Synthetic / genetics
  • Vaccines, Synthetic / immunology*
  • Vaccines, Synthetic / pharmacology

Substances

  • Adjuvants, Immunologic
  • Antigens, Bacterial
  • BCG Vaccine
  • Recombinant Fusion Proteins
  • Tlr2 protein, mouse
  • Toll-Like Receptor 2
  • Vaccines, Synthetic
  • Interleukin-12