The United Status has elected NOT to use adjuvants in the H1N1 and seasonal flu vaccine this year. Why is that an issue? There is a bigger moral question here. Only so much vaccine can be made on any given year. If we don’t use an adjuvant (think of them like an expander) we are reducing the amount of available vaccine for the world. Are Americans obligated to use a additive in a vaccine to help protect people in other countries from the flu pandemic?
The Moral Question…
That is the moral question of a debate over adjuvants — a class of substances that somewhat mysteriously increase the potency of vaccines. So with the world facing severe shortages of vaccine, WHO and some health experts have been calling for the use of adjuvants to stretch the vaccine supply. “We have always argued that using adjuvanted vaccine would leave more vaccine for poor people,” said Marie-Paule Kieny, director of the World Health Organization’s initiative for vaccine research. Wealthy nations have contracted for most of the expected pandemic vaccine production, leaving little for poorer countries. But while Canada and some
European nations will use vaccines containing adjuvants, American officials have decided against it for now. They say that they have enough vaccine and that the safety of the additives has not been proved. “These are products that potentially can be given to millions of healthy people,” said Dr. Jesse Goodman, chief scientist at the Food and Drug Administration. “There is not a known, specific safety danger or issue” with the adjuvants, Dr. Goodman acknowledged. “There’s just more uncertainty.”
Adjuvants and Public Anxiety
U.S. officials fear that using an adjuvant would raise public fears about vaccine safety at a time when their challenge might be about to shift from procuring enough vaccine to persuading people to use it.“If you add what the public would perceive as another unknown there, there’s a concern that people would be reluctant to get vaccinated,” said Dr. Anthony S. Fauci, director of the National Institute of Allergy and Infectious Diseases. One reason that adjuvants are often used is that they can increase a vaccine’s potency against a virus to which it is poorly matched. But the H1N1 vaccine is well matched to the virus, which so far has not mutated.
Early studies suggest that even without an adjuvant, a single injection of swine flu vaccine — rather than the two anticipated — will confer adequate protection on adults and children at least 10 years old. That effectively doubles the number of people who can be immunized, and last week the government said it would make 10 percent of its roughly 200 million vaccine doses available to other countries. Eight other nations are also releasing some vaccine.
If not now…later…
Even if adjuvants do not save the day in this pandemic, experts say they will become increasingly important for vaccines against all manner of diseases. That is because many vaccines now being developed “simply don’t work that well without an adjuvant,” said Dr. Thomas Monath, acting chief medical officer of Juvaris BioTherapeutics, a company developing adjuvants. Vaccines once typically contained a weakened or killed pathogen to spur an immune response. Some newer vaccines consist of only proteins or protein fragments from a pathogen, which makes them purer, safer and quicker to produce. But it turns out that the missing parts of the pathogens help to jolt the immune system; without them, an adjuvant is needed. Companies and academic laboratories are racing to develop adjuvants, “mainly because everyone recognizes the adjuvant could be the make-or-break component of a vaccine,” Dr. Monath said.
Adjuvants had a humble beginning
Scientists are also learning how adjuvants work and how to devise them rationally rather than by trial and error. “For the longest time, adjuvants were sort of a witch’s brew of substances, empirically designed,” said Bali Pulendran, a professor of pathology at Emory University. “What was once a black box is now being illuminated at the mechanistic level by new advances in immunology.”
By the way, the term adjuvant is from a Latin word meaning “to help.” It was first coined in the 1920s by Gaston Ramon, a veterinarian at the Pasteur Institute in France, who observed that horses given diphtheria toxin had a stronger immune response if they had some inflammation at the injection site.
Within a few years, scientists discovered that aluminum salts could prompt an immune response. Alum, as this adjuvant is often called, is now used invarious vaccines, including those for tetanus and hepatitis B. It is a relatively weak adjuvant. But about 80 years after its discovery, it is still the only one used in vaccines the United States.
MF59 adjuvant used in Europe since 1997
A seasonal flu vaccine containing Novartis’s MF59 adjuvant has been used in Europe since 1997. Glaxo’s adjuvant, called AS03, is in a vaccine approved in Europe for use against the H5N1 bird flu, which spurred fears of a pandemic a few years ago. For the bird flu, an adjuvant was crucial because vaccines without adjuvants did not work well in tests and required huge doses. Glaxo’s vaccine required only one twenty-fourth as much antigen, the viral component of the vaccine, as another company’s vaccine that did not contain an adjuvant.
Thinking the swine flu might pose the same problem, federal officials ordered $700 million worth of adjuvant from Novartis and Glaxo. If the adjuvants were used, they would have to be combined with the vaccine before the injection was given. And because the adjuvants have not been approved by the F.D.A., they would fall under a so-called emergency use authorization.
Adjuvant possible side effects
But in the last two weeks it has been learned that the vaccines against the H1N1 virus stimulate a strong response on their own. A single shot containing 15 micrograms of antigen — the same amount used for each strain in a seasonal flu vaccine — should confer adequate protection for most people. Preliminary data from GlaxoSmithKline show that a vaccine with an adjuvant might use only one-fourth as much antigen. But federal officials say the savings are not large enough to offset the possible risks and extra complexity of using the adjuvants. While adjuvants tend to increase the temporary pain, swelling or fatigue caused by a vaccine, the main concern is whether they might cause an autoimmune disease, like rheumatoid arthritis, in which the immune system attacks the body’s own tissues. Some animal studies have suggested that possibility.