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May 10, 2006 -- An immune-boosting substance makes an experimental bird flubird flu vaccine work better -- but probably not well enough to stop a fluflu pandemic.
The finding comes from a human safety study of Sanofi Pasteur's experimental bird flu vaccine. The study explored whether an immune-boosting substance known as an adjuvant -- alum, the only adjuvant currently approved for human use -- might make a bird flu vaccine work better.
That would be a very good thing. Vaccines based on bird flu proteins seem to work only in higher-than-expected doses. Current technology produces these proteins in hens' eggs -- a process that takes a lot of time and effort. Adjuvants are a "dose-sparing" technology that might increase the number of vaccine doses available in an emergency.
"We have tested this vaccine in 300 volunteers," says Melanie Saville, MD, a researcher for the France-based pharmaceutical company Sanofi Pasteur. "The vaccine in different doses and with adjuvant is safe and well tolerated, and we demonstrate an immune response in many individuals. These are encouraging results, but clearly we need more work."
The findings appear in the May 11 early online edition of The Lancet.
The Good/Bad News
Whether the French report is encouraging depends on how you look at it, says Richard Compans, PhD, head of microbiology and immunology at Atlanta's Emory University School of Medicine.
"On the positive side, it has been possible to generate some experimental vaccines that show an effect that may be protective in at least some proportion of recipients," Compans tells WebMD. "On the negative side, the response isn't as strong as one would expect from the current seasonal flu vaccine. There is something special about this [bird flu] protein that makes it less effective as a vaccine component. We don't know what that is. But it doesn't mean it can't be overcome by other approaches."
Saville and colleagues used alum to boost immune responses to a bird flu version of Vaxigrip, a seasonal flu vaccine used in Europe. Two doses of the experimental bird-flu vaccine were given three weeks apart to healthy adult volunteers.
At the highest dose tested, the plain-vanilla version of the vaccine elicited levels of anti-bird-flu antibodies expected to be effective in 52% of volunteers. When given with alum, the high-dose vaccine was 67% effective.
Unexpectedly -- and disappointingly -- the alum adjuvant did not boost immune responses to lower doses of the vaccine. That may be because alum is simply not a very good adjuvant, suggests immunologist David Topham, PhD, of the University of Rochester, N.Y.
"Anything approved for human use is judged on side effects and reactions," Topham tells WebMD. "If it is benign in not causing a lot of negative reactions, it gets approved. Alum is good in that regard. But as an adjuvant, it is not very good at all. It is arguable whether it is better than not using an adjuvant at all, judging from this data. And it didn't work at all at the lower doses."
Dose-Sparing Technology -- or Different Technology?
Fortunately, Topham says, better adjuvants are being tested by his colleague, John Treanor, MD, who leads clinical trials of some experimental bird flubird flu vaccines in the U.S. Saville says Sanofi Pasteur is also exploring the use of better adjuvants.
Of course, better adjuvants mean stronger immune responses -- and probably more side effects.
"There are a lot of adjuvants out there, but whether they can get FDA approval is not clear," Topham says. "If there were a pandemic, we might tolerate some side effects we would otherwise not accept."
Adjuvants are only one way that bird flu vaccines might be improved. In an editorial accompanying the French report, CDC researcher Suryaprakash Sambhara, PhD, and Mayo Clinic researcher Gregory A. Poland, MD, note a few alternatives are now on the drawing board.
Vaccine proteins might be incorporated into immune-stimulating complexes (ISCOMs) or into fat bubbles (liposomes) that stimulate strong immune responses. Or a live-virus vaccine -- such as the currently approved FluMist -- might be adapted for bird flu use.
These strategies may be important, as bird flu has now divided into two separate lineages or clades. Emerging evidence suggests that vaccines against one clade may not work against the other.
But what might be considered "effective" is also open to debate. Saville and colleagues note that seasonal flu vaccines have to prevent infection or disease in order to be effective. A bird flu vaccine, however, might be considered effective if it only prevented severe disease and death during a pandemic.
Even so, the new report shows that bird flu vaccines still have a long way to go before they offer more than a passing chance of protection for a relatively small number of people.
SOURCES: Bresson, J.-L. The Lancet, May 11, 2006; early online edition. Sambhara, S. and Poland, G.A. The Lancet, May 11, 2006; early online edition. Melanie Saville, MD, influenza franchise leader for clinical development, Sanofi Pasteur, Marcy l'Etoile, France. Richard Compans, PhD, professor and chairman, department of microbiology and immunology, Emory University School of Medicine. David Topham, PhD, associate professor of microbiology and immunology, University of Rochester, N.Y.