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

• Published in: Clinical and vaccine immunology Vol. 14; no. 7; pp. 902 - 906
• Main Authors: Wang, Baolin, Henao-Tamayo, Marcela, Harton, Marisa, Ordway, Diane, Shanley, Crystal, Basaraba, Randall J, Orme, Ian M
• Format: Journal Article
• Language: English
• Published: United States 01.07.2007
• Subjects: 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; 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
• ISSN: 1556-6811; 1556-679X
• DOI: 10.1128/CDLI.00077-07

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.