New vaccine cannot be tested against smallpox
Badge of immunity still will be a scar
In a curious twist to an already unusual project, the efficacy of the new smallpox vaccine cannot be tested against the disease it is designed to prevent. Because the disease has been eradicated in humans, and animals cannot be infected with smallpox, the vaccine’s efficacy will never be known absolutely unless those immunized are exposed to smallpox.
"It will be impossible to test the efficacy of the new product," says Lance K. Gordon, PhD, executive vice president of the vaccine manufacturer, OraVax Inc. in Cambridge, MA. "We’re not going to introduce smallpox back into man just so we can see if the vaccine works. So we will be doing it by bioequivalent [testing] and doing some comparative clinical trials directly comparing the old and new vaccine."
New vaccine relies on old
The new vaccine will be a purified derivative of the same strain of cowpox virus that was used in the United States previously, because the old vaccine’s efficacy was clearly demonstrated by direct exposures to those infected. As Edward Jenner observed in late 18th century England, those already infected with cowpox (e.g., milkmaids) do not acquire smallpox. So the old method of vaccine production involved taking a sharp-toothed "comb," dipping it into cowpox virus and then scraping it on the shaved belly of a calf.
"The calf would develop a belly full of blisters, and when ripe, those would be scraped off with a card,’ ground up, and filtered," Gordon says. "It was loaded with calf lymphatic fluid, and any viruses that happened to be in the cow were in there as well. It was certainly not acceptable by today’s pharmaceutical standards."
Immunization with vaccinia occurs through scarification technique, which involves taking the cowpox powder and introducing glycerin to make a suspension, explains John Beecher, RPh, chief of the drug service at CDC and project officer for the smallpox vaccine. "It kind of forms a slurry," he says. "You take this bifurcated needle, which looks like a little pitch fork, and stick it in there. A drop of the slurry or the vaccinia sticks between the bifurcation of the needle through adhesion, because it is kind of thick. Then you take that one drop and you put it on the arm or forearm — where normally you are vaccinated — and you start picking at it with the bifurcated needle, which is sharp enough to break the skin."
Old tech, high effect
As the cowpox penetrates through the skin; the body reacts to the vaccinia, and antibodies begin to form. "Those antibodies are effective in preventing the real variola virus," Beecher says. "It’s old technology, but it was extremely effective."
While the method of immunization through scarification will be essentially the same, the new vaccine will be produced in a mammalian cell culture that contains no animal protein, Gordon says. "It will be a highly purified vaccine but based on the same strain of virus, [which is known as] the New York City Board of Health strain," he says. "This is a live virus vaccine just as the measles, mumps, rubella vaccines and the chickenpox vaccine."
There have been clinical trials to attempt to give the old smallpox vaccine by injection, but it simply does not work, he adds. "A [vaccine] take’ is really the formation of a poc at the site of inoculation, which results in the small round scar that most people over 30 bear," he says. "A requirement for the product is that it gives the same take’ rate, the small poc and scar formation."
While it seems a bit strange by today’s standards, the method of administering the vaccine is easily taught and will not require elaborate preparation, adds D.A. Henderson, MD, who administered smallpox vaccine for the World Health Organization in the 1960s and 1970s. "Certainly, our experience in doing this in the Third World was that even if you just had reasonable technique, you got pretty close to 100% takes," he explains. "It’s not real difficult. We taught villagers to use the bifurcated needle in 15 or 20 minutes of training."
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