Glaxo says its H5N1 vaccine works at low dose

Jul 26, 2006 (CIDRAP News) – An H5N1 avian influenza vaccine made by GlaxoSmithKline (GSK) triggered a good immune response in human volunteers at a much lower dose than other H5N1 vaccines reported so far, which means that hundreds of millions of doses could be produced by next year, the company announced today.

In a clinical trial, 80% of volunteers who received two vaccine doses containing 3.8 mcg of antigen with an adjuvant (a chemical that stimulates the immune system) had a strong immune response, the British-based company said in a news release. A typical dose of seasonal flu vaccine is 15 mcg.

"This is the first time such a low dose of H5N1 vaccine has been able to stimulate this level of strong immune response," GSK Chief Executive Officer J.P. Garnier said in the news release.

By comparison, an H5N1 vaccine developed by Sanofi Pasteur induced a good immune response in 67% of volunteers who received two 30-mcg doses with an adjuvant, according to findings reported in May. The US government is stockpiling the Sanofi vaccine.

Garnier called the GSK vaccine a breakthrough because, with the effectiveness of the low dose, a given amount of antigen will go much further than it would otherwise.

"The meaning of this is that we are going to be in a position, starting later this year, to produce hundreds of millions of doses of an effective pandemic vaccine, so this is a big breakthrough," Garnier said on BBC Radio, as reported today by Agence France-Presse (AFP).

The GSK vaccine was made from an inactivated H5N1 virus collected in Vietnam in 2004, according to Jennifer Armstrong, a GSK spokeswoman in Philadelphia. The vaccine contains a "novel, proprietary adjuvant," the news release says.

The company tested the vaccine on 400 adult Belgians between the ages of 18 and 60, using four different antigen doses, with 3.8 mcg the lowest. Each volunteer received two doses between 3 and 4 weeks apart, Armstrong told CIDRAP News.

Investigators measured the level of antibodies the vaccine produced in the volunteers. This was done by assessing hemagglutination inhibition (HI)—the prevention of the clumping of red blood cells, an effect of the presence of antibodies, according to the release.

More than 80% of volunteers who received 3.8-mcg doses of vaccine with adjuvant had an HI titer of 40, the level considered protective, GSK reported. A good immune response in 70% of vaccinees is one of three immunogenicity criteria used by European health regulators, according to Armstrong.

She said higher doses of vaccine stimulated higher levels of antibodies, but she did not have details on those results. "Our goal is to produce a vaccine that is just immunogenic enough, because we want to protect the maximum number of people," she said.

As for safety, "The vaccine overall was tolerated well, and no serious adverse effects were reported," Armstrong said. "The reactogenicity with the novel adjuvant was slightly more intense than without it, but it was not considered significant."

"There is still a lot more work to be done with this programme, but this validation of our approach provides us with the confidence to continue developing the vaccine, including assessment of its ability to offer cross-protection to variants of the H5N1 strain," Garnier stated in the release. "All being well, we expect to make regulatory filings for the vaccine in the coming months."

Dr. David Nabarro, the United Nations' coordinator for avian and pandemic flu, called the GSK findings "a good and exciting piece of science," according to an Associated Press (AP) report. "But as with all new discoveries, quite a lot of work has now got to be done to establish its place in public health and pandemic preparedness."

Leading virologist Dr. Albert Osterhaus of Erasmus Unversity in the Netherlands also hailed the results as good news, the AP reported. "This is very significant because it shows the principle that this adjuvant might do the job," he said. "With this adjuvant added to the vaccine, provided the rest of the tests are OK, you could make 10 times as much vaccine."

It is uncertain, however, how effective the vaccine would be against H5N1 strains other than the one it was made from. Osterhaus told the AP, "This vaccine will only give protection against this particular H5N1 strain and possibly other strains."

Garnier said he didn't know how much the vaccine would cost because the company still has to "industrialize" its production, according to the AFP report. However, he estimated that the price would be roughly 4 British pounds per dose, or about US $7.35, approximately the same as seasonal flu vaccine.

When asked if any governments have ordered the vaccine yet, Armstrong said, "We're in constant dialog with many governments, but the full magnitude of orders from governments is not known."

She said the vaccine, like conventional flu vaccines, is grown in chicken eggs, a process that takes several months.

See also:

May 12, 2006, CIDRAP News story "Sanofi reports results for H5N1 vaccine with adjuvant"

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