New research center will help advance TB vaccine development

For centuries tuberculosis (TB) has been a major global health problem and the world’s leading infectious killer.  To combat this deadly disease, the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health (NIH), recently announced new contract awards to establish three new centers for immunology research to accelerate progress in TB vaccine development. Three (3) new contract awards provide $30 million in first-year funding to support for the new centers, called “Immune Mechanisms of Protection Against Mycobacterium tuberculosis (IMPAc-TB) Centers.”

Collaboration

The Harvard T.H. Chan School of Public Health (HSPH) was awarded $10,647,647 (NIAID contract 75N93019C00071) on September 25, 2019 and will be led by Dr. Sarah M. Fortune, Associate Member and Director of the TB Program at the Ragon Institute of Mass General, MIT, and Harvard and the John LaPorte Given Professor of Immunology & Infectious Diseases at HSPH; JoAnne Flynn, professor at the University of Pittsburgh; and Henry Boom, professor at Case Western Reserve University. The total funding over the seven-year contract could reach nearly $58 million. The highly multidisciplinary and technologically diverse research team will comprise the HSPH, the Ragon Institute, Massachusetts Institute of Technology, University of Massachusetts Medical School, Boston University, University of Washington, Imperial College London, University of Cape Town, and Makerere University in Uganda, all of which are subcontractors under the Prime contract 75N93019C00071.

The HSPH IMPAc-TB Center will use cutting edge technologies to understand the immune responses that provide protection against TB infection and disease in humans. These findings will be translated to experimental models where they can be more rapidly advanced into clinically relevant findings. Specifically, the IMPAc-TB team will also develop a comprehensive understanding of the immune responses required to prevent initial TB infection, by analyzing immune responses against Mycobacterium tuberculosis (Mtb), as well as immune responses elicited by promising vaccine candidates, in animal models and humans. Finally, they will develop an understanding of the effects of TB co-infections, such as the impact of HIV on immune responses to Mtb infection or TB vaccination, and improve the animal models used to predict Mtb vaccine efficacy in humans.

“Many new technologies, like single cell transcriptional profiling or T cell receptor sequencing, are transforming our understanding of diseases, such as cancer, that are common in the United States but seldom benefit diseases that affect resource-limited countries,” Fortune said. “Through our IMPAc-TB Center, we will be able to bring this arsenal of systems immunology approaches to bear on TB.” The use of these transformative technologies will greatly increase our ability to treat, prevent, and manage diseases common in resource-limited countries.

Dr. Fortune anticipates that this work will identify the features of an immune response that protects against disease. These factors could serve as markers for measuring the efficacy of experimental vaccines in the future. The research could also lead to new targets for experimental TB vaccines.

Researchers at the Ragon Institute, led by Dr. Galit Alter, Professor of Medicine at Harvard Medical School and Ragon Institute faculty member, will examine the humoral correlates of control of Mycobacterium tuberculosis infection in which she has identified unique antibody signatures linked to control of infection.  Through past work with the Bill and Melinda Gates Foundation and the NIH, Dr. Alter has established a suite of assays that shed light on antibody recruitment of the innate immune system and developed a pipeline for engineering antibodies to decipher the mechanism of bacterial control.

TB Facts

TB is caused by Mycobacterium tuberculosis (Mtb), an airborne bacterium capable of spreading from one person to another. According to the World Health Organization, nearly one-quarter of the world’s population carries the Mtb bacteria in an inactive form, called latent TB infection (LTBI). People with LTBI are not symptomatic and do not transmit Mtb to others, but they do face a 5 to 10% lifetime risk of developing active TB disease. Unlike LTBI, active TB is infectious and can be fatal if not treated properly. People who are immunocompromised are at significantly higher risk of developing active TB.

About the Ragon Institute

The Ragon Institute of Mass General, MIT, and Harvard was established in 2009 with a gift from the Phillip T. and Susan M. Ragon Foundation, creating a collaborative scientific mission among these institutions to harness the immune system to combat and cure human diseases. A primary focus of the institute has been to contribute to the development of an effective AIDS vaccine. The Ragon Institute draws scientists and engineers from diverse backgrounds and areas of expertise across the Harvard and MIT communities and throughout the world to apply the full arsenal of scientific knowledge to understanding mechanisms of immune control and immune failure and to benefit patients. For more information about the Ragon Institute, visit www.ragoninstitute.org.

For more information on the IMPAc-TB Center awards please visit: https://www.nih.gov/news-events/news-releases/nih-awards-contracts-advance-tuberculosis-immunology-research.

For more information on the Dr. Sarah Fortune’s research please visit: https://sites.sph.harvard.edu/fortune-lab/.

For more information on the Dr. Galit Alter’s research please visit: http://www.ragoninstitute.org/portfolio-item/alter-lab/.

This article appears on the Ragon Institute website with the permission of the author.

Image description: medical illustration of tuberculosis. Image source: Centers for Disease Control and Prevention.

Ragon Institute Media contact: Corrie Martin, cmartin45@mgh.harvard.edu, 857-268-7074.