ARCHIVED - A Shot in the Arm for National Security

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October 05, 2005— Ottawa, Ontario

Recently, terrorist threats to national security have grown significantly. From bomb sniffing technologies to vaccines that disarm biological agents, several research teams at NRC are working on means to counter terrorism and ensure the safety of Canadians.

NRC scientist handling biological agents in secure research laboratory facility.
NRC scientist handling biological agents in secure research laboratory facility.

As one example, NRC has developed the expertise and the secure facilities necessary to fight lethal biological agents that terrorists might employ against the general public. It is currently working on a more stable, more effective and safer vaccine against Francisella tularensis, a highly lethal bacterium that occurs naturally in Canada. While there is an existing vaccine (an attenuated, live version developed 50 years ago) it suffers from manufacturing and safety problems that prevent its use with humans.

NRC's Infections and Immunity Group, led by Dr. Wayne Conlan, is working both to overcome the regulatory hurdles facing the current vaccine and to develop better alternative live and sub-unit vaccines. This research requires detailed knowledge of how the pathogen causes disease in the body, and how the body's immune system reacts to counter the biological agent.

Secure Facilities to Fight Lethal Biological Agents

Highly infectious biological agents, such as F.tularensismay cause serious or even lethal disease if inhaled.Therefore, research requires highly trained personnel, fail-safe containment facilities, and comprehensive personal protective equipment including full face respirators. Dr. Conlan's work has been pivotal in the development of bio-security guidelines for Canadian laboratories. "Our NRC biological containment lab was the first lab outside of the USA, to gain Centers of Disease Control and Prevention (CDC) approval for work with biodefense agents", notes Dr. Conlan. Such approval is a pre-requisite for funding from the U.S.National Institutes of Health (NIH). To date, NRC has received more than $2.5 million from NIH for its Francisella program.

Bridging knowledge and nations, NRC has been working closely with the Umea University (Sweden) and the National Institutes of Health (United States). The Ministry of Defence (United Kingdom) as well as a Californian company have also recently shown interest in joining the partnership.

Each international collaborator brings important competencies to the project.

The first step is handled by the Swedish group that has unmatched expertise in F.tularensis bacterial genomics. As a result, they are able to develop friendly strains of F. tularensis which lack the genes likely responsible for its virulence. They can also identify bacterial molecules that may act as subunit vaccines. NRC's role is then to test the engineered strains to determine whether they are no longer virulent, but able to stimulate a protective immune response. Plans call for additional pre-clinical testing to be managed by collaborators from the UK. All these steps are required by the U.S. Food and Drug Administration (FDA) to ensure that the vaccine is safe and that it offers the desired protection for humans.

For live attenuated vaccines, a big concern is their ability to revert to full virulence as has happened with the Sabin polio vaccine. However, the methods developed by the Swedish team for the live Francisella vaccines make this virtually impossible. "Live polio vaccines contain altered genes that can repair themselves. However, with Francisella we have deleted entire virulence genes, so our live vaccine will remain safe as well as protective" says Professor Anders Sjostedt from Umea University.

NRC scientist handling biological agents in secure research laboratory facility.

As part of the process, NRC also uses its patented vaccine delivery system to formulate the subunit candidates and test their efficacy. "Our first challenge is to determine which of the 2000 or so proteins of F.tularensis, can best trigger a protective immune response", says NRC immunobiologist, Dr. Wangxue Chen.

Importantly, the researchers must also determine the cost and feasibility of producing the vaccine in sufficient quantities for preclinical & clinical tests. "We have the scientific know-how and the facilities to evaluate these issues," says NRC fermentation specialist Dr. Girish Patel.

Over the coming months, NRC and its research partners expect to design an effective and safe vaccine. Their work will range from genomic manipulation through to pre-clinical testing, while setting standards for biosafety and biocontainment.

Enquiries: Media relations
National Research Council of Canada

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