TORONTO - Canada and the United States may go separate ways when deciding whether powerful boosting compounds called adjuvants should be added to swine flu vaccines, experts suggest.
Canada will likely use adjuvanted swine flu vaccine, says Dr. David Butler-Jones, head of the Public Health Agency of Canada.
But it is not a slam-dunk that regulatory authorities south of the border will clear adjuvanted flu vaccines for a U.S. mass vaccination campaign -- if one takes place -- this fall, some American experts say.
"The risk-benefit of using an adjuvant in a population in which you don't have a lot of data, i.e. younger people . . . has to be balanced against ... what's going on," says Dr. Anthony Fauci, head of the U.S. National Institute of Allergy and Infectious Diseases.
"What's going on in our summer here? In the Southern Hemisphere's winter there? All of those things are going to be playing into the decision of what you're going to use or not use."
Ultimately decisions on whether to license pandemic vaccines with adjuvants will be the job of each country's regulatory agency - Health Canada here and the Food and Drug Administration in the U.S.
They and sister agencies elsewhere will face tough decisions in the weeks ahead, decisions that will likely have to be made with less data than such bodies typically require for the licensure of new vaccines or drugs.
Vaccine expert Dr. John Treanor suspects the FDA may be tempted to take the cautious route, opting to use vaccine without adjuvants.
"I think if you're risk averse, which many government agencies are, you might want to think ... 'Why throw this new thing in the mix that only has the potential to cause problems and create all these headaches for ourselves? Let's do something simple,"' says Treanor, an infectious diseases expert at the University of Rochester in western New York.
"The problem with the adjuvants is it just puts (in) that whole other level of complexity."
Adjuvants are compounds that ramp up the response the immune system generates to a vaccine. At a time when the goal is to vaccinate as many people as possible in the shortest possible time frame, these powerful tools hold a lot of appeal.
Punching up a vaccine's impact means you need less to protect each person. If, for instance, the amount of antigen - the stuff in vaccine that elicits the immune response - could be cut in half, manufacturers could fill orders quicker and stretch available supplies.
The World Health Organization has urged vaccine manufacturers to use what are called "antigen sparing strategies."
It hopes if countries that have pre-purchased pandemic vaccine use dose-sparing approaches, that will free up vaccine for countries that could not afford those kinds of contracts. Canada, the U.S., Britain, Switzerland and Australia are among those that have already purchased pandemic vaccine.
Butler-Jones says given the WHO's request and the fact that Canada's vaccine contractor, GlaxoSmithKline, wants to sell an adjuvanted product, Canada is likely to go that route - as long as the regulatory body is persuaded it is safe.
But adding a new component, such as an adjuvant, adds a significant wrinkle to a regulatory process that has been streamlined to accommodate the frequent strain changes needed to make flu vaccine, others warn.
Because influenza viruses mutate constantly, flu vaccines have to be reformulated regularly - almost on an annual basis. Regulatory agencies have devised a fast-tracking system that allows manufacturers to switch out strains and replace them with new ones as needed, without requiring new licences.
A pandemic vaccine made the same way seasonal flu vaccine is made could piggyback off that system, regulatory agencies have decreed.
But neither Canada nor the U.S. has licensed flu vaccines containing adjuvants. So adding one would erect regulatory hurdles that would either require additional clinical trials - prolonging time to vaccine delivery - or a decision to use the product under "emergency use" authorizations.
"It (adjuvant) makes it a brand new vaccine," Fauci says.
He notes the FDA would have to decide whether it was satisfied by safety data generated in Europe, where one manufacturer, Novartis, has an adjuvanted flu vaccine licensed for use in seniors. "The FDA's going to have to look at it and say: Does this extrapolate to teenagers or people in their 20s or 30s?"
Looming over those decisions will be the long shadow of the 1976 swine flu incident.
An outbreak of swine flu among army recruits at Fort Dix, Md., that year convinced officials they were watching the emergence of a pandemic. Vaccine was made and a mass vaccination program was undertaken in the United States, with 40 million people immunized.
The program was terminated when it was found that a higher-than-expected rate of Guillain Barre syndrome was occurring among vaccinated people. The paralytic condition, which is generally temporary, was recorded in more than 500 people who got the vaccine. And 32 people died.
It is still not known why that swine flu vaccine seemed to trigger such a high number of GBS cases. But as authorities contemplate another mass vaccination to protect against another swine flu virus, they are also wondering what adjuvant might do to the risk of a repeat.
One thought is that adjuvant might reduce the risk, by allowing for smaller doses of vaccine. But if the condition resulted from an immune system response to the vaccine, using adjuvant might elevate the risk.
"The point is ... you can argue the theories in either direction. That's all part of the considerations," Butler-Jones says.
Regulatory bodies are supposed to study evidence and make decisions based on what is best - safest - for their own country's citizens. Still, the special nature of a flu pandemic may add a complicating global equity aspect to the deliberations.
A country that opts not to use adjuvants will need more vaccine per person, leaving less for other countries.
Treanor acknowledges that erring on the side of caution could open the U.S. up to complaints: "Those greedy Americans used it all up because they were too afraid to use adjuvants."
"That's another consideration," he says. "Absolutely."
