Development of a sugar-based meli vaccine

image: Charles Gauthier, researcher at INRS, is a specialist in the chemistry of carbohydrates.
to see Continued

Credit: Josée Lecompte

The threat of melioidosis is real. The bacterium that causes this multi-symptom infectious disease is resistant to antibiotics, making diagnosis and treatment more complex and leading to a mortality rate of up to 50%. Professor Charles Gautier from the National Institute for Scientific Research (INRS) has spent the past decade studying the neglected tropical disease. Having now received over $700,000 in funding from Canadian Institutes of Health Research (CIHR), he is now embarking on preclinical trials for a vaccine in collaboration with professors Eric Deziel and Alain Lamarre.

Burkholderia pseudomallei is found in mud and soils, mainly in equatorial countries such as Australia, Thailand, India and Brazil. When a flood or drought occurs, it can contaminate surface particles that are carried by the wind. “With rising temperatures and the growing risk of natural disasters, studies predict an increase in contamination and areas at risk. You have to be ready,” says Professor Gauthier.

Over the next five years, his team will develop a glycoconjugate vaccine. The sugars expressed on the surface of the bacterium will thus be linked to a carrier protein recognized by the body’s T lymphocytes, the “soldiers” of the immune system which trigger the production of antibodies. Professor Lamarre, a specialist in the development of vaccines, and Professor Déziel, an expert in the microbiology of Burkholderia bacteria, conduct vaccination studies in mice and study the nature of immune responses.

Artificial sugars

The team of scientists will test several versions of the vaccine with different combinations of the three sugar chains, or polysaccharides, expressed by the bacteria. Sugars are promising because they are already targeted by antibodies. Rather than isolating them directly from the bacteria, Professor Gauthier uses imitations of these sugars developed in his previous work. This approach avoids the risk of manipulation of the pathogen.

“We were able to synthesize polysaccharides that mimic those of the bacteria, in addition to being recognized by antibodies. This is pioneering work,” he said. However, the synthesis process will need to be optimized to increase the total sugar yield.

Like a member of the VALIDATE network of the University of Oxford For the development of vaccines against neglected pathogens, Professor Gauthier can count on the help of scientists from all over the world. One of his collaborators is the American researcher Brad Borlee of Colorado State University, who provides him with attenuated strains of Burkholderia pseudomallei. Borlee manufactures the sugars that will be used as controls for sugar “mimickers” in vaccine studies. Gauthier also works with Professor Siobhán McClean of University College Dublin, an Irish researcher studying the proteins expressed by the bacterium. These proteins are also targeted by the immune system and could be used in conjunction with sugars to increase vaccine efficacy.

About INRS
INRS is a university dedicated exclusively to research and training at the university level. Since its creation in 1969, INRS has played an active role in the economic, social and cultural development of Quebec and ranks first for the intensity of research in Quebec. INRS is made up of four interdisciplinary research and training centers in Quebec, Montreal, Laval and Varennes, specializing in strategic sectors: Water Earth Environment, Energy Materials Telecommunications, Urbanization Culture Societyand Armand-Frappier Healthcare Biotechnology. The INRS community includes more than 1,500 students, postdoctoral fellows, faculty members and staff.

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Audrey-Maude Vezina
INRS Communications and Public Affairs Department
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Rachel J. Bradford