A Toll-like receptor-2-directed fusion protein vaccine against tuberculosis.
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.
Wang
Baolin
B
Mycobacteria Research Laboratories, Department of Microbiology, Immunology and Pathology, Colorado State University, Fort Collins, CO 80523, USA.
Henao-Tamayo
Marcela
M
Harton
Marisa
M
Ordway
Diane
D
Shanley
Crystal
C
Basaraba
Randall J
RJ
Orme
Ian M
IM
D000276:Adjuvants, Immunologic / Q000378:metabolism / Q000494:pharmacology; D000818:Animals; D000942:Antigens, Bacterial / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D001500:BCG Vaccine / Q000276:immunology / Q000494:pharmacology; D018664:Interleukin-12 / Q000276:immunology; D008168:Lung / Q000276:immunology / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D009169:Mycobacterium tuberculosis / Q000276:immunology*; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D051195:Toll-Like Receptor 2 / Q000819:agonists / Q000276:immunology* / Q000378:metabolism; D014397:Tuberculosis, Pulmonary / Q000276:immunology* / Q000473:pathology / Q000517:prevention & control*; D014614:Vaccines, Synthetic / Q000235:genetics / Q000276:immunology* / Q000494:pharmacology
D000276:Adjuvants, Immunologic; D000942:Antigens, Bacterial; D001500:BCG Vaccine; D011993:Recombinant Fusion Proteins; C493486:Tlr2 protein, mouse; D051195:Toll-Like Receptor 2; D014614:Vaccines, Synthetic; D018664:Interleukin-12