UB Invention Leads to Discovery of Novel Pathway for TB Vaccine

Terry D. Connell, PhD, professor of microbiology and immunology, developed the novel mucosal adjuvant LT-IIb, which UB patented in 2008.

With its help, he and his colleagues have identified a new pathway that represents a better target for vaccination against tuberculosis.

“This research demonstrates that the most effective vaccination against tuberculosis should target the IL-17 pathway,” he says.

While the traditional tuberculosis vaccine targets—the IFN-y and T helper 1 pathways—are essential in overcoming infection, the new research indicates that they are likely to be less important in vaccination to elicit immune protection against tuberculosis, Connell adds.

The mechanisms that modulate IL-17-based protection are now being studied in laboratories around the world, he notes.

Connell’s lab is leading a study of LT-IIb and similar adjuvants derived from a unique group of bacterial proteins in the type II family of bacterial heat-labile enterotoxins (HLT).

The UB-patented adjuvants have several unique characteristics, Connell notes

“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.

“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.”

As drug-resistant strains of Mycobacterium tuberculosis emerge and more than 1.7 million people die each year from TB, researchers have a strong incentive to develop better vaccines against the disease.

Connell says the next step for this collaborative research is to identify the cellular and molecular mechanisms that underlie the capacity of LT-IIb to induce IL-17-associated immune response to antigens and pathogens.

“Once those mechanisms have been identified, new mutant HLT can be engineered to further optimize the capacity of these adjuvants to enhance desired immune responses to candidate tuberculosis vaccines.”

A big push is underway to develop non-injectable, mucosal vaccines against a number of pathogens, says Connell.

Most, if not all, injectable vaccines need to be stored in the “cold chain” for long periods to maintain their stability, efficacy and safety, he notes. Yet this is very difficult to do in the developing world, where the need for vaccination against tuberculosis is greatest.

“Our mixtures of adjuvants and vaccines can be dried into a powder and stored on a shelf, without refrigeration, until needed,” Connell explains.

The powder could then be sterilized in boiling water, made into a nasal spray and delivered through an atomizer.

Connell is co-author of the new study, which was featured in Mucosal Immunology, a publication of the Nature Group.

His collaborators include scientists from the universities of Pittsburgh, Rochester and Alabama. Pittsburgh’s Shabaana A. Khader, PhD, is lead author.

The National Institutes of Health and the Children’s Hospital of Pittsburgh funded the research.