WASHINGTON (Reuters) - U.S. health officials said on Wednesday they have started human tests of a vaccine against avian flu, which experts believe could kill tens of millions of people if it becomes easily passed from person to person.

The vaccine, made by Sanofi Pasteur, will be tested in 450 healthy adults in Rochester, New York; Baltimore and Los Angeles, the National Institute of Allergy and Infectious Diseases said.

"While there have been relatively few cases worldwide of H5N1 avian influenza infection in humans, the public health community is concerned that the virus will develop the capability of efficiently spreading from human to human and thus create a risk for a worldwide pandemic," NIAID Director Dr. Anthony Fauci said in a statement.

"The initiation of this vaccine trial marks a key advance in our efforts to prepare to respond to an avian flu pandemic."

The vaccine is made from an inactivated H5N1 avian flu virus isolated in 2004. The Phase I study is meant to test the vaccine´s safety -- not whether it protects against the infection that has wiped out millions of birds in Asia and killed dozens of people in Vietnam, Thailand and Cambodia since the end of 2003.

"If the vaccine is shown to be safe in adults, there are plans to test it in other populations, such as the elderly and children," the NIAID said.

"Between January 2004 and March 11, 2005, there were 69 confirmed cases of and 46 deaths from H5N1 infection in humans reported to the World Health Organization," it added.

Normal influenza kills between 250,000 and 500,000 people a year globally but avian flu could be much deadlier.

It is unclear how high the fatality rate is, as people have been found to have been infected without serious symptoms, and people who were believed to have died of other causes were later found to have been infected with bird flu.

Usually, people catch the virus directly from birds such as chickens or ducks. Geese and wild birds and mammals such as cats can also carry the virus.

"To date, there has been a small number of cases where human-to-human transmission of the virus may have occurred. However, public health experts fear that the virus may evolve into one that is more easily transmitted between people," the NIAID said.

"If this were to happen, a worldwide pandemic could follow."

Chiron Corp. of Emeryville, California, also has a U.S. government contract to make an H5N1 bird flu vaccine.

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CIDRAP News

Clinical trial of H5N1 flu vaccine to begin

Mar 23, 2005 (CIDRAP News) – Three universities have begun recruiting volunteers for the first US clinical trial of a vaccine against H5N1 avian influenza, a key piece of the government´s efforts to stave off a potential flu pandemic.

Researchers plan to recruit 450 adults to test the safety and immunogenicity of a vaccine made from an H5N1 virus isolated in Asia in 2004, the National Institute of Allergy and Infectious Diseases (NIAID) announced today.

"The initiation of this vaccine trial marks a key advance in our efforts to prepare to respond to an avian flu pandemic," said NIAID Director Anthony S. Fauci, MD, in a news release.

The phase 1 trial will take place at the University of California at Los Angeles, the University of Maryland in Baltimore, and the University of Rochester in New York. The principal investigators are Joel Ward, MD, at UCLA; James Campbell, MD, at Maryland; and John Treanor, MD, at Rochester.

The vaccine is made by Sanofi Pasteur (formerly Aventis Pasteur), Swiftwater, Pa. The NIAID awarded the company a contract to produce 8,000 to 10,000 doses of the trial vaccine in May 2004.

The trial "will test the vaccine´s safety and ability to generate an immune response in 450 healthy adults aged 18 to 64," the NIAID said. "If the vaccine is shown to be safe in adults, there are plans to test it in other populations, such as the elderly and children."

Last fall Fauci predicted that clinical trials of the vaccine would probably begin in January. NIAID officials have not explained the delay.

Unofficially, 71 human cases of H5N1 infection have occurred in Asia since January 2004, and 47 of the patients died. Nearly all of those cases have been attributed to exposure to sick poultry. The virus has shown little ability to spread from person to person, but if it acquired that ability, experts fear, it could trigger a pandemic.

The clinical trial will be carried out in two stages, according to a University of Rochester news release. In the first stage, a total of 113 people (including 40 in Rochester), will receive two injections 4 weeks apart and will be monitored for side effects. After safety data from the first stage have been reviewed, the remaining 337 people will receive shots and be monitored.

Chiron Corp. also won an NIAID contract in May 2004 to produce pilot lots of an H5N1 vaccine for clinical trials. Information was not immediately available from NIAID on the status of that vaccine or when trials of it might begin.

Besides making H5N1 vaccine for clinical trials, Sanofi Aventis has a government contract to produce 2 million doses of the vaccine for possible use by public health and laboratory workers in the event of a pandemic. The contract is also intended to help the company prepare for mass production in case a pandemic erupts, the NIAID has said.

See also:

Mar 23 NIAID news release
http://www2.niaid.nih.gov/newsroom/Releases/avianfluvax.htm

Mar 22 University of Rochester news release
http://www.urmc.rochester.edu/pr/news/story.cfm?id=745