A new pathway for improving vaccines against tuberculosis has been discovered by microbiologists at the University at Buffalo in collaboration with researchers at other universities, according to a paper in the journal Mucosal Immunology, published by the Nature group.
Lead author on the study is Shabaana A. Khader, PhD, of the Department of Pediatrics, University of Pittsburgh; co-authors are Terry D. Connell, PhD, professor of microbiology and immunology in UB's School of Medicine and Biomedical Sciences and researchers from the University of Rochester and the University of Alabama.
The new pathway was identified in animal studies using LT-IIb, a novel, mucosal adjuvant, developed by Connell, who has shown that LT-IIb dramatically boosts the potency of vaccines that are administered to mucous membranes. Adjuvants enhance the body's immune response against an antigen.
"This research demonstrates that the most effective vaccination against TB should target the IL-17 pathway," says Connell, former director of UB's Witebsky Center for Microbial Pathogenesis and Immunology.
"This observation is in stark contrast to the importance of the IFN-γ and T helper 1 pathways in combating TB infection in the body, which have been the traditional targets for TB vaccines," he says.
"While those pathways are essential in overcoming infection, this published study indicates that they are likely to be less important in vaccination to elicit immune protection against TB," he explains. The mechanisms that modulate IL-17-based protection are now being studied in laboratories around the world, he adds.
Connell's lab is leading the study of LT-IIb and similar adjuvants that are derived from a unique group of bacterial proteins that belong to the type II family of bacterial heat-labile enterotoxins (HLT). These HLT are similar in structure and toxicity to cholera toxin but interestingly, Connell notes, do not exhibit any detectible toxicities when employed as mucosal or systemic adjuvants.
"The adjuvants, which UB patented in 2008 have some unique characteristics," says Connell.
"Depending on the type of adjuvant, one can either enhance the body's ability to make antibodies or enhance the body's cytotoxic response. The great benefit of our type II HLT adjuvants is that these molecules can activate both pathways," he says. "We can direct the type of immune response to the vaccine that is desired, whether an antibody response or a cellular response, simply by choosing one or the other type II adjuvant."