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A British laboratory may have found a fix for the low yield problem that has been plaguing companies making swine flu vaccine, a scientist from the lab revealed Wednesday.
John Wood of the U.K.'s National Institute for Biological Standards and Control said an improved version of the seed strain his lab produced in May seems to generate a virus yield that is on a par with what manufacturers get when they make seasonal flu vaccine.
While Wood cautioned the increased yield has to be confirmed by manufacturers, any improvement would be welcome news. Manufacturers have been clamouring for the new seed strain, which the lab started shipping out Wednesday.
"Oh, they are," Wood said in an interview from Potters Bar, England, where NIBSC is located. "We have a lot of orders in the wings ready to get all the paperwork in place."
Marie-Christine Beauchemin, a spokesperson for Canada's pandemic vaccine contractor, GlaxoSmithKline, confirmed it will obtain the new seed strain.
And Sanofi Pasteur, the world's largest producer of flu vaccine, said it too is eager to give the new seed strain a try.
"That would be a nice improvement," spokesperson Donna Cary said from Sanofi's U.S. headquarters in Swiftwater, Pa., when told NIBSC estimates the new seed strain increases yield 2.5 fold over the best producing vaccine virus currently available to manufacturers.
The first batch of seed strains available to manufacturers produced disappointingly low virus yields.
Manufacturers reported getting somewhere between one-quarter and one-half of the yield with the pandemic virus seed strains as compared to seasonal flu vaccine production.
If left unfixed, the yield problem would have considerably slowed the rate at which vaccine to protect against the pandemic H1N1 virus will roll off production lines in coming weeks and months.
And as recently as two weeks ago, heads of labs that make seed strains - including Wood - were pessimistic they'd be able to find a way to increase the virus yield.
"If it's confirmed, that would be good news," Dr. Marie-Paule Kieny, head of the World Health Organization's vaccine research initiative, said of the better yield associated with the improved seed strain.
Wood said the NIBSC team grew up quantities in 100 eggs, simulating on a minor scale what happens with vaccine production. The yield looked good at that scale, he said, suggesting that is reason to hope the new seed strain will perform well in the hands of manufacturers.
"We do these kind of small scale production runs every year for seasonal flu. And usually it's a pretty good indication of what manufacturers will find. So I'm kind of quietly confident," he said .
Wood, principal scientist in NIBSC's department of virology, said his lab used an unusual approach in its efforts to produce a better yielding seed strain.
Scientists repeated a step in the production process many times more than is usual - that being the growing of viruses in eggs. Eggs are inoculated with viruses, which grow, are harvested and then placed into a new batch of eggs for additional growth.
The process, called passaging, is generally done only a couple of times to allow a seed strain to adapt to growing in eggs.
"Normally we send these viruses out with the minimum of passaging, because we need to get it out quickly, really," Wood said.
But where NIBSC's original seed strain was passaged twice, the new one went through 13 rounds of growth in eggs.
The lab has never passaged a seed strain so many times, Wood admitted. "It was really because of the unusual circumstances that we really didn't have anywhere else to turn."
Another lab has tried a similar approach and it too may have some results as a consequence.
Doris Bucher, head of the laboratory at the New York Medical College in Valhalla, N.Y., confirmed her team has produced three new variants of their original seed strain, all of which appear to produce higher yields than the original. (The team's first seed strain was the best of the original batch made available to manufacturers.)
They were produced with six additional passages through eggs, said Bucher. She suggested in an email that the additional passaging probably contributed to the better yield of hemagglutinin, the major surface protein on a flu virus that is used in vaccine to induce development of virus-specific antibodies.
One potential drawback for manufacturers is the fact that the NIBSC seed strain was created using reverse genetics, a patented process that lets scientists create a hybrid virus made of whatever constellation of genes is desired. In this case, the seed strain has two external genes from the target virus and six internal genes from a flu virus that grows well in eggs.
Bucher's team produces its seed strains using what's called the classical method, in which the target virus and the high-growth virus are allowed to naturally swap genes. Offspring containing the desired gene constellations are then harvested.
Seed strains produced by the classical method are provided free to manufacturers. But royalties must be paid for any vaccine doses made from seed strains created using reverse genetics. The intellectual property (IP) rights are held by MedImmune Inc.. of Gaithersburg, Md., which has said it will waive payment for vaccine that is donated to the WHO for use in low-income countries.
All things being equal, vaccine makers would likely prefer to use a classically produced seed strain. But a significantly improved yield "may be persuasive," Wood said.
Sanofi's Cary agreed. "If you're going to get significantly more doses faster, then certainly that could offset any IP costs."
John Wood of the U.K.'s National Institute for Biological Standards and Control said an improved version of the seed strain his lab produced in May seems to generate a virus yield that is on a par with what manufacturers get when they make seasonal flu vaccine.
While Wood cautioned the increased yield has to be confirmed by manufacturers, any improvement would be welcome news. Manufacturers have been clamouring for the new seed strain, which the lab started shipping out Wednesday.
"Oh, they are," Wood said in an interview from Potters Bar, England, where NIBSC is located. "We have a lot of orders in the wings ready to get all the paperwork in place."
Marie-Christine Beauchemin, a spokesperson for Canada's pandemic vaccine contractor, GlaxoSmithKline, confirmed it will obtain the new seed strain.
And Sanofi Pasteur, the world's largest producer of flu vaccine, said it too is eager to give the new seed strain a try.
"That would be a nice improvement," spokesperson Donna Cary said from Sanofi's U.S. headquarters in Swiftwater, Pa., when told NIBSC estimates the new seed strain increases yield 2.5 fold over the best producing vaccine virus currently available to manufacturers.
The first batch of seed strains available to manufacturers produced disappointingly low virus yields.
Manufacturers reported getting somewhere between one-quarter and one-half of the yield with the pandemic virus seed strains as compared to seasonal flu vaccine production.
If left unfixed, the yield problem would have considerably slowed the rate at which vaccine to protect against the pandemic H1N1 virus will roll off production lines in coming weeks and months.
And as recently as two weeks ago, heads of labs that make seed strains - including Wood - were pessimistic they'd be able to find a way to increase the virus yield.
"If it's confirmed, that would be good news," Dr. Marie-Paule Kieny, head of the World Health Organization's vaccine research initiative, said of the better yield associated with the improved seed strain.
Wood said the NIBSC team grew up quantities in 100 eggs, simulating on a minor scale what happens with vaccine production. The yield looked good at that scale, he said, suggesting that is reason to hope the new seed strain will perform well in the hands of manufacturers.
"We do these kind of small scale production runs every year for seasonal flu. And usually it's a pretty good indication of what manufacturers will find. So I'm kind of quietly confident," he said .
Wood, principal scientist in NIBSC's department of virology, said his lab used an unusual approach in its efforts to produce a better yielding seed strain.
Scientists repeated a step in the production process many times more than is usual - that being the growing of viruses in eggs. Eggs are inoculated with viruses, which grow, are harvested and then placed into a new batch of eggs for additional growth.
The process, called passaging, is generally done only a couple of times to allow a seed strain to adapt to growing in eggs.
"Normally we send these viruses out with the minimum of passaging, because we need to get it out quickly, really," Wood said.
But where NIBSC's original seed strain was passaged twice, the new one went through 13 rounds of growth in eggs.
The lab has never passaged a seed strain so many times, Wood admitted. "It was really because of the unusual circumstances that we really didn't have anywhere else to turn."
Another lab has tried a similar approach and it too may have some results as a consequence.
Doris Bucher, head of the laboratory at the New York Medical College in Valhalla, N.Y., confirmed her team has produced three new variants of their original seed strain, all of which appear to produce higher yields than the original. (The team's first seed strain was the best of the original batch made available to manufacturers.)
They were produced with six additional passages through eggs, said Bucher. She suggested in an email that the additional passaging probably contributed to the better yield of hemagglutinin, the major surface protein on a flu virus that is used in vaccine to induce development of virus-specific antibodies.
One potential drawback for manufacturers is the fact that the NIBSC seed strain was created using reverse genetics, a patented process that lets scientists create a hybrid virus made of whatever constellation of genes is desired. In this case, the seed strain has two external genes from the target virus and six internal genes from a flu virus that grows well in eggs.
Bucher's team produces its seed strains using what's called the classical method, in which the target virus and the high-growth virus are allowed to naturally swap genes. Offspring containing the desired gene constellations are then harvested.
Seed strains produced by the classical method are provided free to manufacturers. But royalties must be paid for any vaccine doses made from seed strains created using reverse genetics. The intellectual property (IP) rights are held by MedImmune Inc.. of Gaithersburg, Md., which has said it will waive payment for vaccine that is donated to the WHO for use in low-income countries.
All things being equal, vaccine makers would likely prefer to use a classically produced seed strain. But a significantly improved yield "may be persuasive," Wood said.
Sanofi's Cary agreed. "If you're going to get significantly more doses faster, then certainly that could offset any IP costs."
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