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

Mycobacteria Research Laboratories, Department of Microbiology, Immunology and Pathology, Colorado State University, Fort Collins Colorado

^* To whom correspondence should be addressed. Email: ian.orme{at}colostate.edu.

	Abstract

A fusion protein designated CSU-F36 was constructed that consisted of acylated Rv1411, a potent Toll-like receptor-2 (TLR-2) agonist, fused to ESAT-6, a well characterized immunogenic protein from Mycobacterium tuberculosis. The CSU-F36 fusion protein strongly induced IL-12 secretion from macrophages, and induced the increased accumulation of CD4 T cells capable of secreting interferon gamma (IFN) 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, cheap new vaccines against tuberculosis.