A team of researchers in the Department of Microbiology, Immunology and Pathology at Colorado State University aim to advance what is known about the complex immune response necessary to prevent tuberculosis disease.

The university was recently awarded a $1.2 million subcontract from the Infectious Disease Research Institute in Seattle under a contract award from the National Institute of Allergy and Infectious Diseases (NIAID). The institute, part of the National Institutes of Health, is leading a new federal initiative to create centers for immunology research to accelerate progress in tuberculosis vaccine development.

The initiative “will be perhaps the most comprehensive pathology assessment of vaccine and TB immunity ever done.”

– Assistant Professor Brendan Podell

The research led by assistant professors Marcela Henao-Tamayo and Brendan Podell is part of a $44.8 million, seven-year award to the Infectious Disease Research Institute, based in Seattle. Rhea Coler, a scientist and senior vice president of preclinical and translational science at the institute, will serve as the principal investigator.

Over the next seven years, CSU may be awarded up to $10.5 million to continue this work.

New vaccines needed

New and improved TB vaccines are badly needed. Over the past 200 years, tuberculosis has claimed the lives of more than 1 billion people — more deaths than from malaria, influenza, smallpox, HIV/AIDS, cholera and plague combined.

Currently, there is only one vaccine for tuberculosis, created nearly 100 years ago. It is known as the BCG vaccine, named for two of the French scientists who led early research into the mechanisms of tuberculosis infection, Albert Calmette and Camille Guerin.

The BCG vaccine protects children from TB disease that may spread to multiple organs in the body. However, the protection this vaccine gives to adults is highly variable. Researchers also do not have a clear picture of what immune factors correlate with protection from vaccination against TB.

“That makes it very difficult, when you’re trying to create new vaccines, to know what you’re aiming for,” Podell said.

Scientists at the Infectious Disease Research Institute have developed a tuberculosis vaccine candidate which has been shown in early-stage clinical trials to evoke a strong immune response. Researchers will continue studies to determine whether the candidate vaccine is effective in preventing infection with tuberculosis-causing bacteria, and whether it may increase the effectiveness of oral therapy to prevent tuberculosis.

The research teams at several sites will mine a great deal of data for this project to develop a comprehensive understanding of the immune responses required to prevent initial infection, establishment of latent infection, and the transition to active TB disease.

They will verify each other’s work using animal models and human subjects, said Henao-Tamayo.

Multidisciplinary team

At CSU, the research will include a multidisciplinary team of at least 20 researchers, students and staff, including Assistant Professors Michael Lyons and Brooke Anderson, Research Scientists Carolina Mehaffy and Andres Obregon Henao, Associate Professor Diane Ordway, and Corey Broeckling, director of the Proteomics and Metabolomics Facility.

Henao-Tamayo, whose TB research has been focused on vaccines, said the project aims to combine expertise from all over the world. It will include experiments to better understand previous research she conducted in collaboration with the late Ian Orme, a CSU University Distinguished Professor, to study environmental mycobacteria, which live in water and soil, and how these organisms may interfere immunologically with the protection that the BCG vaccine provides against TB.

Podell, who earned doctorates in veterinary medicine and pathology from CSU, said the initiative “will be perhaps the most comprehensive pathology assessment of vaccine and TB immunity ever done.”

Podell and Henao-Tamayo said that the award reflects not only the outstanding reputation of CSU’s Mycobacteria Research labs, but also provides a boost of recognition for the program.

“Brendan and I were both trained in these labs, and we’re now leading the charge on this new research,” said Henao-Tamayo.

Additional partners include Oxford University; Public Health England; Statistical Center for HIV/AIDS Research and Prevention at Fred Hutchinson Cancer Research Center; Ragon Institute of MGH, MIT and Harvard; Denver Veterans Affairs Medical Center; National Jewish Health in Denver, and La Jolla Institute for Immunology.

NIAID recently awarded contracts totaling $30 million for the first year to provide up to seven years of support for three Immune Mechanisms of Protection Against Mycobacterium tuberculosis (IMPAc-TB) Centers. The Centers aim to better explain the immune responses required for protection from TB-causing Mycobacterium tuberculosis bacteria. Harvard T.H. Chan School of Public Health and Seattle Children’s Hospital will lead research for the other two centers.

The contract number for this award is 75N93019C00072.

CSU’s Mycobacteria Research Laboratories houses more than 150 scientific investigators, staff and students working on innovations to diagnose, prevent, and treat tuberculosis and related diseases. The team composes the largest group of university researchers in the world focused entirely on this category of infectious disease.

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