A new study shows that a mucosal adjuvant developed by Terry D.
Connell, PhD, could lead to a better vaccine against
tuberculosis.
UB Invention Leads to Discovery of Novel Pathway for TB Vaccine
Researchers have discovered a new vaccine target for
tuberculosis using a University at Buffalo-patented adjuvant that
dramatically boosts the potency of vaccines administered to mucous
membranes.
IL-17 Identified as Better Vaccine Target
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.
Adjuvants Direct Desired Immune Response to Vaccine
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.”
Better Vaccines Could Help Millions
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.”
Vaccine Delivery System Key to Third-World Success
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.
Study Featured in Nature Group Publication
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.
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