Texas Biomedical Research Institute announced Monday it has been awarded a $4.4 million grant from the National Institute of Allergy and Infectious Diseases. The grant will finance testing of a modified tuberculosis vaccine that could prove more effective and provide longer-lasting immunity.
The National Institutes of Health (NIH), of which the National Institute of Allergy and Infectious Diseases is part, will fund the five-year study. Texas Biomedical Research Institute is partnering with Houston's McGovern Medical School on the vaccine investigation, which will be led by Texas BioMed Associated Scientists Marie-Claire Gauduin and Chinnaswamy Jagannath, professor of pathology and laboratory medicine at UT Health Science Center at Houston's McGovern School.
The two scientists aim to strengthen an existing vaccine by adding a novel component that would enhance the body’s immune response. Jagannath's testing on mice has yielded successful outcomes; the next step will be a nonhuman primate study at the Southwest National Primate Research Center on Texas Biomed's San Antonio campus.
Currently, Bacille Calmette-Guérin (BCG) is the only vaccine for tuberculosis (TB) but is not 100% effective and doesn't provide lifelong immunity. It is not used in the United States. Planning assumptions driving the last 10 years of TB vaccine research are being revised in light of new clinical and laboratory data that points to systemic weaknesses in the TB vaccines pipeline.
“Although it works fairly well, the TB vaccine we have only provides immunity lasting about 10 years, so we need a vaccine with longer immunity,” Gauduin said. “It has become important to do this because TB has become very resistant to treatment. The ideal [thing] would be to focus on prevention by giving a stronger vaccine in infancy that would provide longer lasting immunity past adolescence.”
TB is the leading cause of death due to infectious disease, Gauduin said. In 2015, the Centers for Disease Control reported 1.8 million TB deaths worldwide and 9,557 cases in the U.S. The Texas Department of State Health Services (DSHS) Tuberculosis Services Branch reported 1,334 cases of TB in Texas in 2015.
While the course of treatment currently available works well, “it’s toxic and the treatment takes six months,” Gauduin said. “Immunocompromised individuals ... may not be able to handle the treatment.”
TB is particularly problematic when a patient’s immune defenses are down, Gauduin explained, so people with compromised immune systems run a higher risk of contracting the disease. The young, the elderly, and those already fighting a disease like HIV are the most susceptible. TB is also the leading cause of death in HIV-positive patients.
Jagannath and Gauduin aim to strengthen the protective effect of the original vaccine by adding a novel adjuvant, a component added to a vaccine to enhance the body’s immune response. Jagannath and his team have shown in mouse models that the modified BCG vaccine increases the bacteria-killing power tenfold and the length of the vaccine’s protection threefold.
For the next step in the team’s research, Gauduin and her team have developed a model using primates that more closely mimics the disease in humans, enabling them to test the modified vaccine's effectiveness.
“If it works, then we can proceed with clinical trials in humans to develop a better TB vaccine,” Gauduin said.
Ultimately, Gauduin strives to discover a combination HIV-TB vaccine. While TB is treatable, it can also be resistant to drug treatment, which is why finding a more effective, longer lasting vaccine is critical. TB typically attacks the lungs, but can affect other parts of the body and ultimately lead to death if not treated appropriately.
The team will “evaluate the short-term and long-term immune response to this vaccine,” Gauduin said. “This modified BCG vaccine provides an opportunity for the vaccine to boost specialized memory cells, allowing longer lasting immunity.”
A crucial feature of protective immunity is known as immunological memory, the ability of the immune system to respond more rapidly and effectively to pathogens. If successful, the immunological memory for TB will not only be stronger, it will last much longer after a person receives the new vaccine.
“Our ultimate goal is to impact public health by preventing disease and death due to TB," Gauduin said, "especially in our most vulnerable populations.”