TORONTO - Makers of a patch that ramps up the immune system's response to influenza vaccine reported impressive results Thursday, showing that a vaccine against H5N1 avian flu given with the patch raised what are thought to be protective levels of antibodies with a single dose.
The preliminary finding raises hopes a one-dose vaccine-patch regimen might be a possibility in a flu pandemic, eliminating the need to bring every person to be immunized in for a booster dose several weeks after the first or priming dose was given.
That would both streamline pandemic vaccination programs and double the number of people who could be protected with a set amount of vaccine.
Iomai Corporation, of Gaithersburg, Md., announced that in a trial of 500 volunteers, 73 per cent of people who received a large dose of an H5N1 vaccine and the adjuvant patch went on to generate what are thought to be protective levels of antibodies against the virus.
By contrast, 49 per cent of people who got the same dose of vaccine - 45 micrograms - but not the adjuvant or boosting patch generated the same antibody levels. The vaccine used in the trial was made by Solvay Pharmaceuticals.
Experts uninvolved with the research described the findings as exciting, but cautioned against drawing too many conclusions about the possibility of a one-dose vaccine regime based on these findings.
Instead, they focused on the fact that an adjuvant that doesn't come pre-mixed with the vaccine was effective at boosting the response.
"I think that is a very remarkable finding, because in contrast to any other adjuvant system that I know of out there, the adjuvant and the vaccine are not physically in contact with each other," said Dr. John Treanor, director of the vaccine treatment and evaluation unit at the University of Rochester in New York.
"So this is a huge advantage, because in theory this means that the patch can be used with any vaccine. ... You could put the patch over Solvay's vaccine. Or you could put it over sanofi (pasteur)'s vaccine. Or put it over anybody's vaccine ... and in theory you should see an enhanced response."
"And this makes this an extremely valuable tool for pandemic planning."
Additional testing must be done before it can be licensed. But if the patch continues to perform as well, it would offer enormous flexibility and vaccine-stretching potential for pandemic stockpile planners.
"The important thing about this study is its implications for operational value in the field, in developing countries," said influenza vaccine expert Dr. David Fedson.
Fedson, a retired academic living in France, suggested if the patches could be formulated to deliver both vaccine and adjuvant, they could make pandemic vaccine delivery logistically feasible in parts of the world where there is little hope standard vial-and-needle pandemic flu vaccine will ever be available.
The patch is being developed under a US$14.5 million contract with the U.S. Department of Health and Human Services, with the possibility of US$114 million in additional funding.
Iomai CEO Stan Erck said during negotiations for the funding, the department asked Iomai to draw up plans showing how it could manufacture 150 million of the patches for the U.S. pandemic stockpile, should testing show the patches are effective.
"That's the order of magnitude that HHS is thinking right now," Erck said in an interview Thursday.
Iomai tested the vaccine and patch combination in three doses - five, 15 and 45 micrograms. While a response was shown at all doses, 45 micrograms produced the best results, Erck's said.
Given the limited manufacturing capacity for influenza vaccine, authorities hope doses substantially smaller than 45 micrograms can be used during a pandemic. And in fact several other companies have shown vaccines mixed with effective adjuvants can be protective at much smaller doses.
H5N1 vaccine without adjuvants doesn't seem to generate much of an immune response in people. The first licensed H5N1 vaccine, made without an adjuvant by sanofi pasteur, requires two doses of 90 micrograms to achieve a protective response.
Given the past performance of unadjuvanted vaccines, there was some surprise the Solvay H5N1 vaccine protected 49 per cent of the people who got the vaccine alone.
"I think the reason why it's difficult to be very definitive about this is because the responses they're measuring to unadjuvanted vaccine suggest that their assay is somewhat more sensitive than the assays that have been used in other (companies') studies," Treanor said, adding more testing must be done before one could say a one-dose vaccine-plus-patch regimen might work.
"I think there's additional information that you'd like to have before you reach this conclusion. But it's certainly promising and I think a very important goal."
Erck said more work will now be done to try to tweak dosages with an aim to finding out if less vaccine could safely be used on each person. And additional work should provide more evidence with which to gauge whether a single dose with the patch would work, he said.
"That's what we hope for. But even if it turns out that the judgment is that it needs to be a two-dose vaccine in any case, it still looks like putting an adjuvant patch on top of it improves the response at two doses."
