05/09/2013 07:08 EDT | Updated 07/09/2013 05:12 EDT

Canada not planning H7N9 bird flu vaccine studies; will watch US results: PHAC

TORONTO - Canada currently has no plans to ask its pandemic flu vaccine manufacturers to make trial batches of vaccine to protect against the new H7N9 bird flu, senior officials of the Public Health Agency of Canada have revealed.

While the U.S. government has said it will ask several of flu vaccine manufacturers to start growing up batches of serum against the new virus this summer, Canada will watch, wait and learn from the work the U.S. does, the officials said in an interview with The Canadian Press.

"What we need to do in the international research-scientific community, the public health community is to complement each other. If the U.S. is doing something, we don't need to do it necessarily," explained Dr. Frank Plummer, head of the National Microbiology Laboratory in Winnipeg.

Dr. John Spika, director general of the public health agency's center for immunization and respiratory infectious diseases, said doing this early work is more crucial for the United States, which will have to make a decision about whether to use an adjuvant with H7N9 vaccine, if the virus causes a pandemic. An adjuvant is a product that boosts the immune response to a vaccine, typically allowing a smaller dose to have a protective effect.

The U.S. has not used adjuvants with flu vaccine before, but Canada used adjuvanted vaccine during the 2009 pandemic. And when the federal government signed new pandemic vaccine contracts in 2011, it stipulated it wants adjuvanted vaccine the next time it needs pandemic vaccine.

"So this step of doing some early clinical trials looking at immunogenicity is really going to be critical for the U.S. go-forward process. Whereas here in Canada, we've already made a decision on what kind of vaccine we're going to use. It's going to be an adjuvanted one," Spika said.

Canada's main flu vaccine producer, GlaxoSmithKline, has a proprietary adjuvant, a product called ASO3. Sanofi Pasteur, which is Canada's secondary provider, does not currently have a licensed adjuvant that can be used with its flu vaccine.

The new flu virus, which hit the world's radar at the beginning of April, has already caused 131 infections in China and Taiwan — which has reported a single case — and 33 of the infected people have died. H7 flu viruses have not circulated widely in people before and it's believed virtually everyone would be vulnerable to this new bird flu, if it fully adapts to person-to-person spread.

The emergence of the virus is causing sleepless nights in pandemic preparedness circles. While it provokes severe disease in people, it causes no discernible illness in birds at this point. So finding where the virus is and how people are getting infected has been an enormous challenge. As well, the virus has some mutations that suggest it is partially adapted to infecting human respiratory tracts; experts say it appears to infect people more easily than other known bird flu viruses.

Making matters worse is that fact that if the virus triggers a pandemic and vaccine is needed, there are multiple reasons to believe that producing an effective H7N9 vaccine could be hugely difficult. Those problems were spelled out in a prospective article the Journal of the American Medical Association published online late Thursday.

The article, by researchers from the Center for Infectious Diseases Research and Policy at the University of Minnesota, outlined the long lead time for making flu vaccines, the modest protection offered by current seasonal vaccines and the limited but alarming data on vaccines against H7 viruses.

Over the past few years the U.S. government has financed several small clinical trials testing vaccines for other H7 viruses, viruses like the H7N7 that infected around 90 people in the Netherlands in 2003 and the H7N3 that infected two people in British Columbia in 2004.

The results have been dismal. Flu vaccine experts say H7 viruses appear to be the least immunogenic (immune-response inducing) of the bird flu viruses. In fact, in studies using killed virus vaccine — the type of vaccine used in seasonal flu shots — massive doses of serum failed to produce a protective response in most people.

Seasonal flu shots contain 15 micrograms of antigen for each strain they protect against. In the H7 vaccine studies, 12 times that much vaccine (given in two shots) did not raise antibody levels to the degree that is considered protective.

"The bottom line is that it didn't do very much," flu vaccine expert Dr. John Treanor, chief of infectious diseases at the University of Rochester (N.Y.) Medical Center, said of the previous H7 vaccine trials. "In fact only a handful of people even had a measurable (immune) response."

If even 90 micrograms of vaccine are needed to protect a person against the H7N9 virus, "global annual manufacturing capacity will be approximately 757 million doses," said the JAMA paper, the lead author of which is Michael Osterholm, director of the University of Minnesota centre.

"This is less than 15 per cent of the global need and much of it will not be available until six or more months after manufacturing begins," Osterholm and his colleagues wrote. "Adjuvants may augment vaccine capacity, but development of an adequate global vaccine supply will remain an unprecedented challenge."

The U.S. Department of Health and Human Services does a risk assessment whenever a new flu virus emerges; the deliberations involve deciding on whether a trial lots of a vaccine should be made and tested.

In this case, the decision has been made to go ahead with H7N9 vaccine clinical trials. The U.S. government has set aside $25 million for the development of vaccine seed strains and small vaccine batches for clinical studies, Gretchen Michaels, director of communications for the office of the assistant secretary for preparedness and response, said in an email. The current plan is that the manufacturers — who are currently still making next winter's seasonal flu vaccine — will start making the H7N9 vaccine in early summer.

In Canada, no such work is currently envisaged.

And the company which has the lion's share of Canada's pandemic flu vaccine contract, GlaxoSmithKline, said Thursday it has not yet taken possession of a seed strain for H7N9 vaccine. Janet Grdovich, communications manager for GSK Canada, said at this point she cannot say whether the GSK plant at Ste-Foy, Que., will started working with the H7N9 vaccine seed strain.

"GSK is taking routine preparedness measures and will respond appropriately to the situation, depending on how or if it develops further," she said.

Spika acknowledged that the available evidence suggests that an H7N9 vaccine might be poorly immunogenic in people and that figuring out what a protective dose would be — even with an adjuvant — will take study. "And we're going to be able to get that information from the U.S. trials," he said.

Spika and Plummer did not, however, rule out the possibility that Canada might do some work on H7N9 vaccines in the future.

"If it's scientifically required, we will do it," Plummer said.

"We're obviously monitoring the situation," Spika added. "It may well be, if this strain continues to emerge, and based on the results coming out of the United States, that we may want to move in that direction. But not at this point."