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If ya wanna make a flu vaccine, ya gotta break a few eggs. Actually, over tens of millions. The current "hen oviduct bioreactor technology" (a.k.a., using eggs) takes up to nine months in its entirety. That means if health authorities goof in choosing the viral strains they think will be prevalent in the winter, or we have a flu-shot shortage like this year, it’s too late to start a new batch. People get sick; people die.
But two biotechnology methods will change that. One is reverse genetics, which precisely replicates only the viral genes that must be grown into vaccine. The other is the multiplier of that vaccine in mammalian cells. Both scramble the egg technique and slash manufacturing time, allowing a quick and life-saving turnaround in production of new doses.
With the present 50-year-old method, each February virologists from the World Health Organization (WHO) and elsewhere sample various populations to guess which three flu strains will be prevalent next winter. These are then grown in one set of eggs to make "seed vaccine," which is then injected into those tens of millions of other eggs and then processed into the final product.
It’s not just that this slow process makes the February guess a final one; it also makes it likelier to be wrong. Merely providing the WHO a few extra weeks to collect samples could make the difference in predicting the proper strains.
Normally an improperly chosen strain (as was the case last year) can still produce a semi-effective vaccine, because there are still genetic similarities between the two. But if there’s a radical "shift" in the strain, the vaccine would be worthless. We would then suffer another pandemic such as that which killed 70,000 Americans in 1957-58 (the equivalent of 100,000 with our current population. There were two other such shifts in the 20th Century, and some scientists think we’re overdue for another.
Reverse genetics will speed up things at the early stage of vaccine making. "That means instead of employing actual virus you’re just cloning the genes, explains Richard Webby, a virologist at St. Jude Children’s Research Hospital in Memphis. "The process of getting the proper strain in a chicken age is fairly random and you may have to start over," he told me. In fact it may be necessary to repeatedly start over, losing precious time with each effort.
Reverse genetics means accurate replication first time, every time. And it’s done in less than a week. Already Webby’s lab and others have engineered the so-called "bird flu" from Southeast Asia that the media regularly – and rather hysterically – tout as a possible cause of the next pandemic.
In extreme cases, says Webby, "Reverse genetics could enable re-engineering a virus that otherwise would be so dangerous that few manufacturers can safely work with it." So the process could mean not just getting a vaccine faster but getting one at all.
While human testing won’t begin until next year, it’s encouraging that other labs and companies such as MedImmune of Gaithersburg, Maryland, maker of the nasal spray vaccine FluMist, are also experimenting with engineered flu viruses.
Flu vaccine without eggs is truly worth crowing about.
The second speed-up will replace those tens of millions of eggs. Lab technicians will just go into the freezer, push aside the ice cream and popsicles, pull out the cells, and grow them quickly in vats in whatever-sized batches they need. No chickens need apply.
Many biotech companies are using such cells. Netherlands-based Crucell in partnership with Aventis Pasteur of France is using human ones, others are working with canine (MDCK) cells, while California-based Chiron Corporation and SoloHill Engineering of Ann Arbor are working with those from monkey kidneys. Aventis Pasteur has already used monkey cells to make an FDA-approved polio vaccine.
SoloHill, in conjunction with the Massachusetts branch of ID Biomedical Corp., is in the second of three phases of human clinical trials. According to the National Institutes of Health, their cellular method is superior to the egg technique because it requires much less manufacturing space, because some flu strains are so toxic they can’t even be grown in eggs, and because cells can multiply far faster than hens can lay. In fact, SoloHill has multiplied cell batches eight-fold in just six days.
Further, those with allergies to chicken eggs have nothing to fear, nor does anyone else with allergies, because the final product contains no animal tissue. For many of us, that’s nothing to cluck at.
Some companies experimenting with the animal-cell technique also believe their final product will be closer to the actual virus than vaccine hatched from a chicken egg, although the FDA says that’s not yet proved.
SoloHill CEO David Solomon says he thinks final approval of the technology is still "three or four years" off. Reverse engineering may not be implemented for even longer. But either system can be implemented independently. Nevertheless, we think we can cut the entire vaccination production process "to 90 days or less," Solomon told me.
Thus a new strain might not be discovered until the flu season actually begins, yet we could still have a vaccine ready before it peaks. This could save thousands of lives in a U.S. epidemic. With a pandemic, it would save tens of thousands here and perhaps even millions worldwide. That seems worth the price of putting lots of chickens in the unemployment line.