TORONTO - It may take substantially longer to make the full amounts of swine flu vaccine countries have contracted to buy because efforts to improve the yield of the vaccine seed strains aren't bearing fruit, experts say.
Three of the laboratories involved in the work are sounding increasingly pessimistic that the yield problem can be fixed in the short term. Vaccine manufacturers have reported they are getting between 50 per cent and 75 per cent less vaccine with the new H1N1 virus as they do when they make seasonal flu vaccine.
"It's not looking very bright at the moment," John Wood, principal scientist at Britain's National Institute for Biological Standards and Control, said in an interview Tuesday.
"In effect, it means if we continue like this, manufacturers will have to keep on producing (pandemic) vaccine for longer to make the number of doses needed."
The flu laboratories at the U.S. Centers for Disease Control have made three new seed strains and are in the process of completing the paperwork needed to ship them to the manufacturers.
The head of the CDC's influenza division said while the new vaccine candidate viruses are growing well in the hands of her scientists, there's no guarantee they will produce a better yield when manufacturers start to work with them.
Dr. Nancy Cox said the issue isn't simply about growth, but also about how well the vaccine viruses hold up during the various steps of the manufacturing process.
"I think it is possible we won't have a better yielding virus," she admitted from Atlanta.
"(But) I think that it's still too early to say how this will impact the amount of vaccine that's available."
Each flu virus has its own characteristics and vaccine makers are accustomed to working with new strains, fine-tuning processes to try to coax maximum yield from a virus.
A spokesperson for vaccine giant Sanofi Pasteur said the company feels it hasn't yet exhausted efforts to improve the yield of the seed strain for the pandemic vaccine. Still, Len Lavenda suggested Sanofi doesn't expect those efforts to fully correct the problem.
"Although we think it's too soon to project what the final yield will be, we anticipate it will remain lower than seasonal vaccine yield," Lavenda said from Sanofi's headquarters in Swiftwater, Pa.
"Certainly if the yield doesn't increase it means it will take longer to produce the vaccine. (But) I think at this point in time we remain hopeful that we'll be able to increase the yield and think it's premature to throw in the towel, so to speak."
The various companies making pandemic vaccine have been working with a seed strain produced at New York Medical College in Valhalla, N.Y. Its laboratory pioneered the process of engineering vaccine viruses to maximize growth decades ago and scientists there have produced many of the vaccine seed strains used since.
Its first swine flu seed strain was overwhelmingly viewed as the best yielder by vaccine manufacturers. But even at that manufacturers said they got about half of the yield generated with seasonal flu production.
Doris Bucher, who heads the lab, says her team is trying other options, but they haven't seen anything promising yet. And she's heard manufacturers' efforts aren't paying off either.
"Usually they tweak it and it grows better. But it hasn't responded to tweaking. ... (That's) the feedback I'm getting."
Seed strains are hybrid viruses that have the surface genes of the virus the vaccine is meant to protect against merged with the internal genes of an old flu virus that is known to grow well in eggs.
Typically those hybrids - called reassortants - are made up of six genes from the high-growth virus with two genes from the target virus, which in this case is the new H1N1.
Seed strains can be made by two different processes. One, called the classical method, involves co-infecting growth medium with the two types of viruses and letting them swap genes on their own. The other involves a patented process called reverse genetics that essentially allows scientists to piece together the desired constellation of genes.
Bucher's first seed strain was made using the classical method, which means any vaccine made from it wouldn't require manufacturers to pay royalties for the seed strain.
But the new CDC-produced seed strains were made using reverse genetics. If manufacturers switch to use one of them, royalties for every dose of vaccine sold will be due to the U.S. vaccine company MedImmune, which holds the patent.
Bucher said her original seed strain was made with three genes from the swine flu virus and five from the high-growth virus. Her team is now trying to see if a six and two constellation would work better.
But she and others admitted the yield problem may be due to something inherent in the swine flu viruses.
"It possibly is," admitted Wood, whose lab also generated seed strains in the first round of production.
"This is unusual, having all the labs who usually do this work and there still being a less than satisfactory outcome. Usually, we get at least one virus which is good. Average to good. And this time none of them are."
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