By David Brown
Washington Post Staff Writer
Thursday, July 27, 2006; A11
The giant pharmaceutical company GlaxoSmithKline reported yesterday that it has made an experimental vaccine for bird flu that appears to work at a dose far lower than even the familiar seasonal flu shots.
The vaccine contains an adjuvant, or immune booster, along with a killed version of the H5N1 influenza virus. It allows a smaller-than-usual amount of virus to stimulate a protective level of antibodies in the bloodstream. That, in turn, would permit public health authorities to stretch the supply of vaccine during a pandemic and cover more people.
"It worked beyond our wildest dreams," said Bruce Innis, a physician who heads the viral vaccine division of the drugmaker's U.S. operations.
The company is one of several that have been testing various adjuvants in experimental vaccines against the influenza, which is spreading worldwide in poultry and has infected 232 people, killing more than half. The nature of GSK's adjuvant is secret; the company would not even provide its in-house name.
The positive finding came from a just-finished study in Belgium of 400 volunteers 18 to 60 years old. GSK compared four different doses of H5N1 vaccine containing adjuvant with the same doses without the additive. The company provided only bare details of the results, which have not been peer-reviewed or published yet.
A vaccine is by far the best form of defense against H5N1 avian flu. At the moment, that strain passes very poorly from person to person, but health officials fear it could evolve that capacity, triggering a pandemic.
If the GSK findings hold up, they will prove that a "dose-sparing" vaccine against bird flu is possible. That could have major public health implications, in effect instantly expanding the world's limited but growing capacity to make flu shots.
"I think it's an important step in the direction of where we need to get in order to adequately address preparedness for pandemic flu," said Anthony S. Fauci, director of the National Institute of Allergy and Infectious Diseases at the National Institutes of Health.
The annual flu shot elicits an immune response in most people with 15 micrograms of inactivated influenza virus. An NIH-sponsored study last year found that it took 90 micrograms of H5N1 virus to produce a response -- and even then only half of people were protected. A vaccine requiring that much virus material (known generically as "antigen") would be of no practical use, as not enough could be made to effectively protect the population during a pandemic.
The GlaxoSmithKline study found that with its adjuvant, as little as 3.8 micrograms of H5N1 antigen was enough to elicit a protective response in more than 80 percent of people.
The company also tested 7.5-, 15-, and 30-microgram doses. All protected more than 80 percent of the volunteers, although Innis would not say what the highest level of protection achieved was.
With the vaccines that did not contain adjuvant, "there was not a response that would allow this product to be licensed" even at the highest dose, he said. Generally, authorities require that at least 70 percent of people get a protective level of antibodies.
To make the vaccine, GSK used a strain of H5N1 that circulated in Vietnam in 2004, causing many deaths. A key unanswered question is whether the antibodies against that strain would protect a person against other strains.
The company plans on testing the blood serum from the immunized volunteers against more recent strains from Indonesia and Turkey, and also against older strains from the first H5N1 outbreak in Hong Kong in 1997.
If the antibodies in the serum neutralize those viruses, that would support a strategy of giving H5N1 vaccine to people now in the hope it would protect them at least partially against future strains, even if they are somewhat genetically different strain.
GSK would not say when it hopes to submit the vaccine to the Food and Drug Administration for approval, but Innis said the company plans to start making industrial quantities of H5N1 vaccine later this year.