Immune Response

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Constant Evolution
“We were originally set up as a spin-off from the veterinary college to act primarily as a technology transfer organization — to take ideas from academia, do the proof of concept studies and then transfer them to industry,” explains Andrew Potter, PhD, who has been with VIDO for more than 20 years and currently serves as its associate director (research).
The focus on agriculture and food animals was a natural fit for the centre, but VIDO shifted its focus when current director and CEO Lorne Babiuk, PhD joined the organization.
“Lorne had a fairly clear vision of where he saw things going,” Potter explains. “He thought we should be doing a lot more basic research on our own, as opposed to simply taking stuff out of academic departments.”
Potter describes VIDO’s approach as “basic research, but managed research,” noting that the group’s mandate was clearly laid out by Babiuk.
“Lorne’s vision was to conduct fairly high-risk activities,” Potter says. “We weren’t interested in doing the same things that companies were doing — they do that fairly well on their own. We really wanted to define technologies that would be of value 10 years into the future, and in the 1980s, of course, that was (in) biotechnology.”
VIDO focused its efforts on recombinant vaccines, eventually developing a total of seven commercially available products (largely for cattle, swine and poultry) and generating a spin-off company, BioStar Inc., which was ultimately acquired by Novartis Animal Health Inc. (Basel, Switzerland).
After these successes, another shift was in the works in the mid-1990s.
“It became very clear in the mid-1990s that we were becoming an organization that was developing platform technologies, and those platform technologies had applications in animal health as well as human health,” Potter explains. “Therefore, we decided ‘why not marry the two and start looking at human applications?’ Humans are just another animal species at the end of the day.”
During this period, VIDO began programs centred on vaccine formulation and delivery — which continue to this day — as well as conducting work on food and water safety.

Baby Steps
Perhaps VIDO’s most high-profile project is its Neonatal Immunization Program, one of 43 projects supported by the Grand Challenges in Global Health program. The undertaking is supported by a grant from the Bill and Melinda Gates Foundation (Seattle, WA), and involves the improvement and development of vaccines for newborns, with a focus on pertussis, commonly known as whooping cough, as a model disease.
“When you’re looking to vaccines for the newborn there’s a number of challenges that you have to overcome, which in fact is the reason why current vaccines are not very effective,” explains Volker Gerdts, PhD who manages the neonatal immunization project.
The international team is working to overcome the challenges posed by newborn immune systems, which are not fully developed and are supplemented by maternal antibodies.
“The immune system is immature, so basically you get protection from these passively transferred antibodies,” Gerdts says. “That’s very nice, but the problem with that is that if you have a vaccine that you want to use early on in life to induce a response, these antibodies can actually interfere with your vaccination (and) make it less efficient.”
Gerdts says that he and his fellow researchers are attempting to develop platform technologies that will induce positive immune responses in newborns. They are currently working with a reformulated pertussis vaccine combined with novel immune stimulators, which would be administered mucosally.
“We are combining what we call the innate immune response, the immune response that takes place right away after infection or immunization . . . with what we call the acquired immune response, which usually kicks in after about a week or two weeks,” Gerdts says.
“By using these immune modulators, we are beginning to understand more and more that the innate immune system is actually almost as important as the (acquired immune system), so we are choosing molecules that will stimulate both.”
Given the Gates Foundation’s focus on the developing world, the team is also mindful of reducing the number of inoculations needed for an effective vaccination.
“We’re trying to get away from multiple immunizations, which are not possible in developing countries,” Gerdts explains. “That’s why still, every year, about 400,000 babies die in the developing world — because they don’t have access to multiple immunizations. For this Gates project, the focus really is to develop an effective vaccine formulation that allows a single-shot immunization . . . and therefore, hopefully, better vaccine coverage in those countries.”
Receiving the Gates grant was an important milestone for VIDO. Gerdts says that it was the organization’s work on a novel porcine (pig) disease model for pertussis that gave VIDO the edge amongst 1,500 submissions from across the globe.
“We can basically do exactly the same (thing) we are hoping to do in infants,” he says. “We can go in and we can vaccinate newborn piglets on the first day of life, and then we can infect them with the bacteria after two weeks and look at the protection,” he says.
Despite VIDO’s prominent role, Gerdts is quick to point out that co-operation is the key to the project’s success.
“The unique thing about this is that it’s a true collaborative research project,” he says. “We have collaboration all across the world — that was one of the requirements by the Gates Foundation, that there is actually an institution from the developing (world) involved,” noting VIDO’s partnership with the International Vaccine Institute in Seoul, South Korea, as well as Canadian counterparts in British Columbia and Nova Scotia.

A Natural Selection
Another of the organization’s current projects focuses on the genomics of innate immunity. The study is a collaborative effort involving Bob Hancock, PhD and Brett Finlay, PhD of the University of British Columbia (Vancouver, BC) and Fiona Brinkman, PhD of Simon Fraser University (Burnaby, BC), and aims to identify key innate immunity pathways.
The project had an initial scope of $29 million and included two industrial partners: Pixis Genomics, in Chicago, Ill., and Inimex Pharmaceuticals Inc., from Vancouver, with Inimex handling the human side and Pixis handling the animal side. Pixis has since pulled out of the project, and Inimex has acquired all of its rights and funding obligations moving forward.
“(The project) takes a functional-genomics approach to looking at mucosal immunity,” Potter explains. “Nobody had really done that before, in a comprehensive fashion, and so it (is) a very large project.”
“If we can identify critical pathways in innate immunity . . . we’ll have very specific targets for intervention in a variety of infectious diseases.”

Potter points out that VIDO’s emphasis on food animals led to the development of more complex animal models. The traditional mouse model was replaced with more complicated animal systems that, according to Potter, give VIDO the upper hand.
This advantage becomes clear in light of recent developments in infectious diseases. With animal-linked diseases such as SARS, West Nile virus and Avian flu making headlines over the past few years, VIDO is poised to be in an advantageous position.
“The bottom line is these diseases come up at a fairly routine rate, and more often than not — in fact, 79 per cent of the time for new diseases — these are related to animal sources,” Potter explains.
Despite the high profile of these emerging diseases — all of which are bio-containment Level 3 organisms — a shortage of suitable facilities makes it difficult to investigate them on an immediate basis. That’s where VIDO’s new International Vaccine Centre (InterVac) will come into play.
“There are some Level 3 laboratories around, but in terms of animal facilities, there aren’t a lot in Canada,” Potter says. “The ones that are here tend to be booked long in advance, so it’s difficult to get into them in a timely fashion. Of course, if you’re looking at emerging diseases, timing is everything.
“What we proposed to the Canada Foundation for Innovation (Ottawa, ON) was to build a facility that would be a very large, Level 3 animal facility capable of handling anything from a mouse up to a cow, as well as a set of Level 3 laboratories to go along with it.”

Prairie Perks
While the immediate rewards of InterVac would be reaped by VIDO, surrounding facilities, such as the University of Saskatchewan’s (Saskatoon, SK) veterinary and medical schools, would also benefit, as would international parties.
And while the effects of VIDO’s efforts will be felt far beyond Saskatchewan’s borders, the centre is still based in one of Canada’s smaller biotech markets. But Potter says there’s no place VIDO would rather be. Aside from the obvious agricultural connections, the province has been backing VIDO every step of the way.
“Any time you get into building containment facilities, you’d better have the support of your community, surrounding area and province before you go ahead, and the people of Saskatchewan have been absolutely remarkably supportive,” Potter says.
In fact, the city of Saskatoon is providing financial support for InterVac, which is scheduled to open its doors in 2009.
“I dare say you might not get that type of support in one of the larger centres,” Potter adds.
And that support makes VIDO feel right at home.