New Contract Will Advance Tuberculosis Research

A federal contract awarded to Seattle Children’s will establish a new center to study tuberculosis. Source: Getty Images.

Seattle Children’s Research Institute is one of three recipients of $30 million in first-year-funding provided by the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health (NIH), to establish centers for immunology research to accelerate progress in tuberculosis (TB) vaccine development.

The awards provide up to seven years of support for three Immune Mechanisms of Protection Against Mycobacterium tuberculosis (IMPAc-TB) Centers to uncover the immune responses needed to protect against TB infection. In addition to Seattle Children’s, other IMPAc-TB centers will be led by the Infectious Disease Research Institute, also in Seattle, and the Harvard T.H. Chan School of Public Health.

On the Pulse learned more about the significant research that will be funded by this award which has the potential to provide up to $83 million to the Cascade IMPAc-TB Center, led by Dr. Kevin Urdahl, a TB researcher in Seattle Children’s Center for Global Infectious Disease Research.

Q: Why is this research needed?

The Cascade IMPAc-TB Center will be led by Dr. Kevin Urdahl, a TB researcher in Seattle Children’s Center for Global Infectious Disease Research.

A: We desperately need a new vaccine that works more effectively against TB. The current BCG vaccine has been in use for almost 100 years. While it provides some protection in infants against serious forms of the disease and saves thousands of lives every year, it has not curbed the TB epidemic.

Despite widespread vaccination with BCG globally, TB remains the world’s biggest infectious killer with 1.6 million people dying from the disease each year. The big barrier to developing a better vaccine is that we don’t really know how protection against TB works.

Q: How will this research help move the needle?

A: What’s clear is that TB is very different from other diseases for which vaccines have been effective. The approaches that have worked for these other diseases just don’t work for TB. This research will approach TB differently by integrating research in animal models in the lab and in humans to determine how immunity against TB is achieved. Approaching it in this way will provide a constant feedback loop – taking what we learn from the lab to the clinic and then what we learn from the clinic back to the lab – that I think is what the field really needs to move forward.

To do this we will collaborate with the University of Washington, Fred Hutchinson Cancer Research Center, Oregon Health & Science University, Beth Israel Deaconess Medical Center in Boston and three clinical sites in Africa.

It’s exciting because we’re going to be using cutting-edge scientific approaches that just haven’t been used to study TB before. We’ll use single cell biology to look at individual cells at sites of infection to characterize the immune cells that correlate with protection. We’re also going to be using advanced microscopy to image immune cell interaction and map the organization of immune cells that associate with protection.

Q: What do we hope to learn from this research effort?

tuberculosis bacteria
Bacteria known as Mycobacterium tuberculosis cause tuberculosis. Source: Getty Images.

A major problem that has impeded the development of an effective TB vaccine is that we haven’t known what type of an immune response an effective vaccine should target because our understanding of how immunity against TB works is inadequate. In humans, although there have been several suggestions that protective immunity is possible, it has been difficult to identify which individuals are protected and which are not. In animal models, immunity against TB has been incomplete and its relevance to protective immunity in humans has been unclear. Thus, a major barrier to studying protective immunity against TB in both animal models and humans is that it has been difficult to define protection in a meaningful way.

In the last 5 years, several breakthroughs in the TB field have shown for the first time that TB vaccines can provide clearly defined protection. In humans, we have the first example of a vaccine that, when used in combination with BCG, provides better protection against active TB than BCG alone. In animals, we now have experimental vaccines that can either eradicate the bacteria that causes TB from the body or prevent the bacteria from initiating infection in the first place.  We did not know such protection was even possible 5 years ago!

Now that we know it’s possible, we need to understand how the experimental vaccines achieve this effect. That’s a major goal of this research. By using new animal models that simulate human TB infection more closely, we can determine what mediates protection. Then we can leverage tools now available to us to process the data and, for the first time, find what creates protection. This new information will help us identify potential vaccine targets and pave the way for a more effective TB vaccine.

Q: How did Seattle successfully compete for this important award?

A: We’re fortunate because the Center for Global Infectious Disease Research has intentionally built a pediatric infectious disease research program that attacks problems from a different perspective. We have immunologists, microbiologists, systems biologists – people from all different backgrounds and expertise that can converge on attacking the immunology of TB or vaccines for TB from very different angles.

This integrated approach made it possible for us to successfully compete for this contract that will advance the field. Along with many others in the TB community, I have believed this is where the field needs to go, so it’s rewarding to have the opportunity to lead this work.