Aug. 11, 2009— -- While drug makers prepare a swine flu vaccine in anticipation of a possible outbreak this fall, one of the issues yet to be resolved is whether the shots will contain an adjuvant.
"It's something that allows the immune system to respond with higher levels of effectiveness," said Dr. David Fedson, formerly a professor of medicine at the University of Virginia and former medical director for the pharmaceutical company Aventis Pasteur.
Adjuvants can include various forms of aluminum and are typically used with other vaccines in the United States, including vaccinations for hepatitis A and B, diphtheria-tetanus-pertussis and Haemophilus influenzae type b (Hib). In a flu vaccine, the adjuvant would be a water-oil mixture.
By using them in various vaccines, doctors hope to reduce the amount of the vaccine itself that is needed.
"Hopefully, in the future, they're going to lead to the ability to get a better immune response with much less vaccine," Dr. Andrew Pavia, chair of the public health committee of the Infectious Diseases Society of America and a professor of professor of pediatrics at the University of Utah, said in an interview with ABC News last September.
The ability to stretch a supply of swine flu vaccine -- and an adjuvant's ability to help to do that -- is not trivial. Fears have arisen about whether there will be enough swine flu vaccine available. Adjuvants can allow dosing to be much smaller.
For example, Fedson points to trials for a bird flu vaccine in which 90 micrograms of an antigen -- a flu virus's "signature" that allows for an immune response -- could be reduced to 3.75 micrograms when an adjuvant was introduced, effectively enabling 24 times more doses.
"By adding an adjuvant, you gain what is known as an antigen sparing effect," Fedson said.
While flu vaccine doses typically use 15 micrograms of antigen, adjuvants could increase that significantly.
"Being able to produce four times as many vaccines is a huge advantage in terms of public health," Fedson said.
At the same time, vaccines have long been plagued by safety concerns -- whether legitimate or not -- and the use of adjuvants is only likely to add to that. No flu vaccine approved for use in the United States has ever contained an adjuvant.
"It wasn't felt to be necessary, because the flu vaccines that have been used for decades in this country … were rather broadly protective," said Dr. Anthony Fauci, director of the National Institute of Allergy and Infectious Diseases. "We felt that the immune response of the vaccine was pretty good to begin with."
Safety and Availability Fears May Clash
Fears surrounding the swine flu vaccine are often attributed to the vaccine for the 1976 swine flu epidemic when a few hundred people came down with Guillain-Barré syndrome after receiving the swine flu vaccine.
While the bad publicity led to the halting of the vaccine program after 40 million Americans had received the vaccine, no link has ever been proven between the vaccine and Guillain-Barré.
But concerns about what might happen with the vaccines remain, and the addition of adjuvant is likely to add more fuel to the fire.
The initial trials of the swine flu vaccine for the United States will be with the unadjuvanted form, while later trials with an adjuvanted form may take place if deemed necessary.
"We'll probably be looking at that in a few weeks in case we don't get as good a response with the unadjuvanted vaccine," Fauci said. "We don't plan to start any trials on adjuvants at least until we get a bit into the adjuvanted trials."
He said that a mild flu season would likely mean the trials of a vaccine with an adjuvant would not get started. But a swine flu that returned quickly and spread quickly might force their usage.
"It's something that we're keeping as a contingency in case we need to use them," Fauci said. "Right now, the main priority is to test the unadjuvanted vaccine."
Should an adjuvant be needed, however, Fauci said there is little question that it would be safe.
"We're more cautious than when we use something that we've used every year for decades," he said, noting, however, "the Europeans have used these same adjuvants for a long period of time with a … reasonable safety record."
But if adjuvants were to be used, they would likely be used in older people, where they have been tested, rather than children.
"There's not a lot of data on adjuvants in young kids -- even from the Europeans," Fauci said.
Good Domestic Public Health, Bad International Public Health?
Officials do not expect a shortage of swine flu vaccine. "We don't anticipate that we will run out, but it's possible," Fauci said.
But while Americans may not face a shortage, Fedson said that not using adjuvants is a problem from an international perspective, although it makes getting the vaccine approved in the United States easier.
"From the regulator point of view, this will be the least onerous pathway to follow to get it approved," he said. "I think that's the path of easy regulatory approval, but whether it meets the public health needs of the world and the nation is another matter."
The problem, he said, is that the concerns for approval are for the individual. But even if the United States has enough, failure to use adjuvants means that doses for developing countries -- who don't have their own vaccine production capacity -- are unavailable.
Even more, said Fedson, because the swine flu virus has not been experienced by many Americans, they will need two doses of vaccine instead of one to develop immunity.
Describing the distribution methods for swine flu vaccine "a boutique approach to global public health," Fedson called them "an approach which will not make much difference for the people in 90 percent of the world, who will not have access to vaccines or antivirals."