Preventing a Comeback
GlycoNet researchers work to limit the spreads of tuberculosis
By Marie-Christine Houle
Most people in North America may be under the illusion that tuberculosis is an antiquated disease belonging to Victorian times. But tuberculosis (TB) is alive and well and ravaging many regions of the world. In 2018, an estimated 10 million people fell ill with tuberculosis. The disease was responsible for 1.2 million deaths in 2018 alone.
The multifaceted problem of TB has led the medical and research communities to sound the alarm. Many are working to find ways to prevent and treat this contagious disease. Bacillus Calmette–Guérin (BCG) vaccine, the only approved vaccine to protect against TB, is not effective in adults. TB outcomes also worsen in people suffering from illnesses that affect the immune system, such as HIV.
Dr. Anne Villela, a Post-doctoral Fellow in GlycoNet Investigator Dr. Lori Burrows’ lab at McMaster University, is among those who have made it their mission to identify effective ways to prevent TB. Along with Burrows and a team of GlycoNet researchers, including Dr. Zhou Xing, Villela is investigating the use of glycosylated pilins as a vaccine candidate for tuberculosis.
“I like that this project can make a tangible difference,” says Villela, who is conscious that she has her work caught out for her. “It can take around 10 years for a vaccine to go from preclinical trials to the market,” she adds. Villela is not in it for the short term. She does hope that a concrete solution to this health crisis will be uncovered sooner rather than later.
Burrows, Xing and Villela and their team are making headways towards preventing TB. They are evaluating type IV pili found in Pseudomonas aeruginosa as a vaccine against TB. Some type IV pili from P. aeruginosa are modified with a glycan found in the bacterium that causes TB. Since P. aeruginosa is a fast-growing bacterium and pili is highly expressed on the bacterium’s surface, the necessary quantity of this protein can be easily isolated through shearing and formulated into a vaccine. Mouse studies are underway to evaluate the protective efficacy and immunogenicity of the pilin-based vaccine. They hope that immunization using glycosylated pilins will enhance anti-TB immunity by stimulating the production of antibodies against the bacterium that causes TB. In the near future, Villela and her colleagues are looking to combine the pilin-based vaccine with Ad-Hu5Ag85A – an adenoviral-based vaccine developed by the Xing lab at McMaster University that is currently in clinical trials – to elicit both humoral and cellular immune responses, as both are important to control TB.
Originally from Brazil, Villela’s passion for research was ignited in 2004, when one of her former molecular biology professors, invited her to come work at his biopharmaceutical company. She enjoyed working with biopharmaceutical research and development and pursued a Master in this field. Villela’s increasing interest for tuberculosis and infectious diseases led her to pursue a PhD in biochemical characterization and genetic studies of an enzyme as a drug target for tuberculosis in Dr. Diogenes S. Santos’ lab (CPBMF, PUCRS, Brazil). Looking for new challenges and to further her knowledge in tuberculosis and infectious diseases, she connected with Burrows and Xing who had received funding from GlycoNet to study the pilin from P. aeruginosa as a vaccine candidate for TB. This funding was instrumental to Villela finding her way to the Burrows’s lab.
Villela understands the important interdependency of industry and academia. She has dabbled in both and is keen to conduct research that addresses major health issues head-on. Before leaving Brazil, she contributed to many projects in the field of tuberculosis research. “I’m glad that I was able to implement new techniques, train people and contribute to research in Brazil,” she says. “The sense of achievement made it easier to leave the country, looking for new challenges.”
Asked if she would once again leave her home to come to Canada, Villela has a clear and inspiring message for young researchers who are contemplating a move: “Leave. Do something else. Learn new things. It was challenging but it was one of the best things I have ever done. I look forward to continue working towards the development of a vaccine that might be approved for the prevention of TB, impacting the life of thousands of people across the globe.”