TORONTO - A flurry of innovative vaccine trials is in the offing as governments and regulatory agencies prepare for the probable launch of mass swine flu vaccination programs in the fall.
The results of the trials could determine whether people with egg allergies can be offered pandemic (and regular) flu vaccine, whether pandemic and seasonal flu shots could be given at the same time and whether one company's vaccine can be given with another's adjuvant, a compound that boosts its potency.
Vaccine manufacturers are either unable or unlikely to undertake the complicated studies required to answer these questions. Governments will fund the work instead.
Infectious diseases expert Dr. Anthony Fauci says the goal here for organizations like the U.S. National Institute of Allergy and Infectious Diseases - which he heads - is to fill key knowledge gaps for vaccine regulators.
"What are they going to need that somebody else can't do?" Fauci explains.
Some of those priorities will be aired Thursday in Washington when the U.S. Food and Drug Administration's vaccine and related biological products advisory committee meets in a session on clinical trials for pandemic vaccines.
Vaccine manufacturers will do the basic testing, work designed to assure regulators and would-be recipients that their vaccine is safe and likely to protect against the pandemic strain, an H1N1 virus of swine origin.
But there are many other key questions. In fact, the list is too long to tackle in its entirety in the limited time available.
So discussions between planners and regulators over the past few weeks have led to a paring down of priorities. In the case of the U.S., it's not yet clear which studies have survived the cut.
However, Fauci says his institute will green-light one looking at whether the pandemic vaccine - to protect against the new H1N1 virus - could be given at the same time as seasonal flu vaccine, which protects against three types of flu viruses including a different H1N1.
Co-administration, as it is called, would make the logistics of pandemic vaccine delivery much easier - if the pandemic vaccine is ready in time. But would giving people vaccines that protect against two different H1N1 viruses at once actually undermine the effort by weakening the response to one or both?
"As an immunologist, I don't think you're going to have any trouble with that. But you don't know," Fauci explains.
"Would presenting two different H1N1 antigens to the body at the same time result in antigenic competition? On the other hand, we could be surprised and giving them together might enhance the response to both."
In Canada, plans are underway to try to test whether people with egg allergies could be given flu shots containing vaccine produced in eggs. Currently that is considered unsafe and is not done.
With some manufacturers moving to grow their vaccine viruses in cell culture, that may be less of a problem in the future. But for now egg-based production still generates the lion's share of of the global flu vaccine output. Canada's entire supply will be egg-based vaccine.
Dr. Scott Halperin, a vaccinologist from Dalhousie University in Halifax, says a newly formed, federally funded research network hopes to get ethics approval to test the assumption it is unsafe to give people with egg allergies flu shots.
The goal will be "to basically look at what is the real risk, and to immunize individuals under very carefully controlled (circumstances)," says Halperin, principal investigator of the Public Health Agency of Canada/Canadian Institutes of Health Research Influenza Research Network.
"That is a real concern," he says of the current position on people with egg allergies. "You can't leave a whole segment of the population without access to protection."
Another question regulators in the United States and possibly some other countries need answered relates to the use of adjuvant. Specifically, they'd like to know whether one of the powerful new adjuvants made by companies like GlaxoSmithKline and Novartis could be used with antigen (vaccine) made by a company that currently doesn't market adjuvants, such as Sanofi Pasteur.
This type of study - called "mix and match" by those involved in the planning - won't have an impact in Canada. GSK has the contract to provide all of Canada's pandemic vaccine and is producing adjuvanted pandemic flu shots.
And the findings may not be put into application in the U.S. either, if it is shown that swine flu vaccine on its own will produce an adequate immune response. U.S. officials have repeatedly hinted they may forgo use of adjuvant if it isn't needed to get the job done.
But the U.S. has planned for contingencies, buying bulk adjuvant in case there isn't enough vaccine and supplies need to be stretched. Having some evident for the FDA that mix and match would work means the backup plan could be activated if needed.
"Nobody's going to do that (trial) but us," Fauci says. "I can tell you that for sure."