One shot? Two shots? Experts deliberate on where to go with flu shots

TORONTO - One shot? Two shots? What to do with flu shots?

That may sound like a bad riff on a Dr. Seuss story, but it is actually the dilemma facing flu vaccine experts meeting this week in Melbourne, Australia.

Scientists from laboratories that form the World Health Organization's influenza collaborating centres network have gathered, as they do twice a year, to pore over global virus circulation patterns and reports of how similar or distinct - from an immune system point of view - new strains are compared to their recent ancestors.

The goal: To advise vaccine manufacturers and countries that buy seasonal flu vaccine which viruses are likely to be most problematic in the coming flu season, so vaccines can be tailored to protect against them. This meeting, the results of which are expected to be announced later this week, is tasked with selecting the strains for next winter's flu shots for the Southern Hemisphere.

But this isn't just another strain selection meeting. Flu is in a state of flux and it's not at all clear what kind of vaccine the Southern Hemisphere will need.

More pandemic vaccine to protect against the new H1N1 virus? Seasonal vaccine to protect against three families of viruses that have been making the rounds for decades, even though one or two of them may have stopped circulating by the time the vaccine is made? Or a new seasonal vaccine including the pandemic virus, either in addition to or instead of one of the seasonal strains?

"I don't envy them having to make some of these decisions," says Dr. Walter Dowdle, who headed the flu lab at the U.S. Centers for Disease Control during the last pandemic, the 1968 Hong Kong flu.

"It's going to be a bit more challenging this year than normal years," agrees Dr. Nancy Cox, who now heads the CDC's influenza division.

It takes months to make, distribute and administer flu vaccine, which is why experts are meeting in late September to decide on vaccine that will be injected into arms next June.

Because the picture of what's going to happen with the interplay of pandemic and seasonal flu viruses still hasn't come into focus, the WHO has told the experts to just select the strains and leave decisions on formulations of vaccine to another WHO advisory group, which will meet in late October.

The hope is by then flu's future path will be clearer. But Dowdle thinks the world may have to wait until the coming Northern Hemisphere flu season is done before it learns whether the pandemic virus is going to push the seasonal influenza A viruses out of the playground or share the turf with one or both of them.

In previous pandemics for which the causative virus is known - a very short list - the emergence of a new flu virus led to the obliteration of the influenza A virus that preceded it. The H1N1 virus that caused the 1918 pandemic disappeared when H2N2 materialized in 1957, triggering the Asian flu pandemic. When H3N2 appeared in 1968, H2N2 viruses stopped circulating.

But this time there's a twist.

In 1977, H1N1 viruses similar to those that had circulated before the 1957 pandemic reappeared. It's believed the re-emergence was the result of a lab accident in Russia. Whatever the source, those H1N1s managed to reseed themselves though they didn't cause a pandemic because there was so much immunity to H1N1 viruses in people over about age 30.

Ever since, two influenza A viruses - H3N2 and seasonal H1N1 - have co-existed in humans.

Since the swine flu H1N1 virus erupted late last winter, seasonal influenza A viruses have been few and far between. But they're not yet gone. In North America, pandemic viruses make up more than 96 per cent of circulating flu viruses. But will seasonal viruses make a comeback in what is our traditional flu season? Science doesn't currently have the tools to answer that question.

"We know a lot, but we don't know quite enough," says Dr. Marie-Paule Kieny, who heads the WHO's vaccine research initiative.

She suggests a number of options will be hashed out in the coming weeks and months, including keeping the pandemic vaccine separate and putting a pandemic component into the seasonal shot.

The latter could lead to the recommendation to make a flu vaccine that covers four strains - an idea that makes experts and industry alike groan. Or three, with the pandemic H1N1 replacing the seasonal H1N1, perhaps. Or in the best case scenario, if it seems both influenza As have been replaced, the recommendation could be to make a bivalent (two component) vaccine that protects against the pandemic strain and one influenza B virus.

"There are a number of options and each option has an impact on our production capacity," says Pascal Barollier, a spokesperson for Sanofi Pasteur, the world's largest flu vaccine producer.

"So we are compiling the options, looking at the impact on production capacities. And that will be part of the discussion and the recommendation that we might have, if we are asked to give an opinion as one of the manufacturers. But to date it's too early for us to comment on what would be the ideal solution."

Figuring out what would be ideal won't be easy. Ask several experts and you'll get several answers.

Dr. Scott Halperin, a vaccinologist at Dalhousie University in Halifax, thinks the pandemic vaccine should remain separate while the pandemic virus is mainly sparing the elderly. (It's believed that as the virus changes to be able to find new people to infect, it will broaden its scope.) It's too soon to incorporate it into the seasonal shot, he says.

"To me, you certainly don't want to do that the first year, you probably might not even want to do that the second year."

But Dr. Kathy Neuzil, who directs the influenza vaccine program at PATH, a global health non-profit organization based in Seattle, says having to organize two separate flu shot campaigns is not something public health should be saddled with for long.

Dowdle agrees. "You don't want to be stuck with two vaccines. The quicker you can get it into a combined formulation, the better off you are as far as administering the vaccine."

-Follow Canadian Press Medical Writer Helen Branswell's flu updates on Twitter at CP-Branswell