Research Profile - A bacterial solution to asthma?
Dr. Tobias Kollmann
New CIHR-funded research at the University of British Columbia shows that a vaccine based on the bacterium behind listeriosis prevents mice from getting asthma.
Using a weakened strain of Listeria monocytogenes – the food-borne bacterium that causes the infection listeriosis – a University of British Columbia researcher has developed a vaccine that prevents asthma in mice.
"It's such an absolute and qualitative difference that we thought it was too good to be true, so we went back and repeated it many more times to make sure we're not missing something," says Dr. Tobias Kollmann, whose work is funded by the Canadian Institutes of Health Research (CIHR). "But no, it's a fully preventive vaccine. It works 100%."
At a Glance
Who – Dr. Tobias Kollmann, Clinician Scientist at Vancouver’s Child & Family Research Institute, Assistant Professor, Department of Pediatrics, Division of Infectious & Immunological Diseases, Vaccine Evaluation Centre; University of British Columbia
Issue – Studies have linked the development of asthma to exposure to allergens very early in life. Until now, preventing exposure to allergens has been the best defence against getting asthma.
Approach – Dr. Kollmann has developed a vaccine based on a weakened strain of the microbe that causes listeriosis. It appears to switch off the allergic response in newborn mice, preventing asthma for the rest of the mouse’s life.
Impact – While the vaccine has only been tested on mice, it holds promise in preventing – and possibly treating – asthma. It also may have applications in preventing allergic responses to allergens such as peanuts and could be useful in foiling pertussis and other infections.
Dr. Kollmann and his colleagues gave newborn mice a vaccine prepared from Listeria bacteria incapable of causing any harm to the young pups.
"We chose newborn mice because there is evidence suggesting that the risk for developing asthma is highest early in life," says Dr. Kollmann. "The reason isn't quite clear, but the newborn immune system seems to be prone – if exposed to allergens – to develop an asthma-like allergic response. If exposed to allergens early in life you are more likely to develop asthma."
Dr. Kollmann's theory is that the Listeria vaccine causes the newborn's immune system to shift away from the allergic response to an anti-allergic one that persists for the life of the mouse. "It's one shot at birth and you're protected from asthma," he says.
His preliminary findings appeared in December in the journal Vaccine, with more publications on the way. Meanwhile, he is testing the vaccine to see if it can cure asthma in mice that already have the condition.
"That's probably the more realistic approach for future applications, and the initial data look promising," says Dr. Kollmann. He also thinks the vaccine could be useful in preventing peanut allergies and infections from various pathogens.
The vaccine, which can be administered orally and doesn't require refrigeration, has "Trojan Horse" qualities: it does its work, and then quietly dies and disappears.
"The only trace it leaves behind is it doesn't allow the mouse to get asthma any more," says Dr. Kollmann. "That's the beauty of it."
He is also looking into the possibility of producing a synthetic version that would not carry any risks of "live" Listeria bacteria. "There's something about Listeria replication that does the trick," says Dr. Kollmann. "That's what we're trying to figure out right now."
While he and his colleagues are "literally working day and night to make this work and get this out," he urges caution in interpreting the results.
"This is in neonatal mice in one asthma model. By no means do I want to say this is going to work in every human for every asthma-causing trigger. It's clearly something that needs to be slowly expanded so that it gets to the level where it could be translated into larger animal studies and eventually tested in human studies."
Dr. Volker Gerdts, the Associate Director Research of the Vaccine & Infectious Disease Organization at the University of Saskatchewan, sees Dr. Kollmann's work as very important in the fight against asthma.
"Knowing the work and the calibre of (Dr. Kollmann's) research, I'm very hopeful," says Dr. Gerdts. "His research is also focused on understanding the neonatal immune system. He's developing a vaccine platform, based on the Listeria bacterium, and he hopes he can vaccinate against common diseases that each year are still causing millions of young children to die. He has a very promising approach."
"We are excited with the results we have so far. But clearly it's early days. There are so many sensational stories about discoveries that then tank and you never hear from them again. That's not our style. Until we have data that goes beyond the artificial system of a mouse, it would not be in anyone's interest to tout this as a cure for all."
-- Dr. Tobias Kollmann