Researchers at the McGill University Health Centre (MUHC) recently gained ground on the global effort to eradicate tuberculosis. This spring, the Research Institute of the MUHC opened a new level 3 laboratory that will provide its scientists with a safe environment to study candidates for a new tuberculosis (TB) vaccine.
The facility will allow MUHC researchers to compete with the best in the world. Although there are other level 3 laboratories in Quebec, including one at the Royal Victoria Hospital site of the MUHC, they are not classified for research. “To do the research we want to do, the closest would be at Saranac Lake (New York) or in Hamilton (Ontario),” says Marcel Behr, a microbiologist, and an assistant professor of medicine at McGill University. “It puts us on a level playing field.”
The laboratory is specially built to ensure that none of the bacteria used in the research leave the lab alive. Each room in the laboratory is under negative pressure, which means that air can only flow into the lab, preventing airborne particles, such as bacteria, from escaping. Only a select group of people will be allowed to enter the laboratory and each will have to follow a detailed set of rules designed to prevent anyone from being infected by the bacterium in the lab, or from carrying it out with them. Once it is in operation, researchers will be required to don work suits, boot covers and three pairs of gloves and leave their civilian clothes in an anteroom.
Behr, who joined the MUHC in 1999, could be called a vaccine historian. That year, with colleagues from Stanford University, Behr chronicled the life of the Bacille Calmette-Guerin (BCG) vaccine at the molecular level. They found that after the original bacteria left the Pasteur Institute in Paris and took up residence in other vaccine laboratories around the world, it began to change. In the 90 years since the vaccine was developed, little bits of the bacterium’s genetic material have been snipped out and lost or mutated, which may explain why the vaccine has mixed results in different parts of the world.
But for Behr these genetic changes are also signposts, identifying ways that the vaccine can be improved. Behr has developed what he believes will be a Band-Aid solution by patching the damaged part of the vaccine with a gene. “We took something that was gone and have put it back,” he explains.
“Unlike all these other (new) vaccines (being developed), the BCG vaccine has human proof of principle,” he says. “A new product can never say that there were thousands who got it and thousands who didn’t and that there were different outcomes, that less people got TB.”
“We have an excellent candidate and have known about it for a year, but it has not been tested in an animal model,” he says. The candidate vaccine was recently sent to a lab in Colorado to be tested. “It would be nice to do it locally, but, for now, if we can plug it into someone else’s pipeline, we can get a more robust result.” In the future Behr will be able to do this type of work in the level 3 laboratory at the MUHC.
At a more local level, Behr has also carried out a number of studies that look at TB infection in different groups within Canada. The Arctic Inuit communities continue to have high rates of tuberculosis. Behr and his colleagues analyzed a decades’ worth of tuberculosis samples from Inuit communities in Northern Quebec. He found that transmission is widespread and ongoing within the community, despite measures to eradicate the disease. It showed how difficult it can be to control the disease.
Within Montreal, he found that many different strains arrive from many different countries. “It provides a window into the global TB reservoir,” says Behr. He has studied the differences among the tuberculosis strains that are identified in new Montrealers, evaluating whether those diagnosed with the disease carried it from another country or caught it here. Most, he says, are due to the former. “Although there continue to be TB cases in Montreal, the medical community is doing a great job at controlling them,” says Behr.