UTHealth Researchers Identify Molecule That May Lead to Chagas Disease Vaccine

Researchers from the University of Texas Health Science Center at Houston (UTHealth) School of Public Health, in collaboration with the National School of Tropical Medicine at Baylor College of Medicine, have identified a molecule expressed by Trypanosoma cruzi (T. cruzi) that may facilitate the parasite’s evasion of the host’s immune system. The paper was published online recently in the American Journal of Tropical Medicine & Hygiene.

“In this paper, we describe a protein, Tc24, that T. cruzi likely uses to hide from the immune system, allowing it to persist for decades undetected until it is too late. Thirty percent of infected individuals develop chronic Chagas disease that can result in cardiomyopathy that is untreatable,” says Eric L. Brown, PhD, senior author and associate professor in the Department of Epidemiology, Human Genetics and Environmental Sciences at UTHealth School of Public Health.

Tc24 is a B-cell superantigen that is a member of a family of proteins that can delete populations of B cells capable of secreting antibodies with the ability to neutralize the parasite.

In previous research, Brown found that by slightly chemically modifying superantigens, they are capable of stimulating the immune system rather than suppressing it.

“If we could modify the molecule, we could mount an immune response that would prevent that organism from disseminating and causing infection. This could help both people and canines who are infected with Chagas disease or are at-risk for infection,” says Brown, who is also a faculty member in the Center for Infectious Diseases at the School of Public Health.

Chagas is a parasitic disease that affects more than 8 million people across the world, including approximately 300,000 people in the United States, according to the Centers for Disease Control and Prevention. Triatomine bugs, also known as a kissing bug, transmit the T. cruzi parasite. Most human infections come from contact with the feces of an infected kissing bug, usually after it has bitten a person, although congenital, bloodborne, foodborne and waterborne transmission can occur. Kissing bugs received their name because they usually bite people near their mouth while they sleep.

At present there are no vaccines or gold-standard diagnostic tests for Chagas disease, according to Brown. Two medications exist for the disease, nifurtimox and benznidazole, but they have not been approved by the Federal Drug Administration for use in the United States and can cause adverse health effects, Brown said.

In the next phase of research, Brown said he hopes to chemically modify the molecule and conduct pre-clinical trials to see if the immune-evading process can be reversed.

Additional co-authors from the School of Public Health include first author Sarah M. Gunter and Heather T. Essigmann. Baylor College of Medicine researchers of the study included Kathryn M. Jones, DVM, PhD.; Bin Zahn, MD; Kristy O. Murray, DVM, PhD; Melissa N. Garcia, MPH; Rodion Gorchakov, MS; Maria Elena Bottazzi, PhD; and Peter J. Hotez, MD, PhD. The study was titled “Identification and Characterization of the Trypanosoma cruzi B-cell Superantigen Tc24.”

Source: University of Texas Health Science Center at Houston