Aug. 21 (Bloomberg) -- Vaccines being prepared for a possible influenza pandemic need to keep pace with changes in the bird flu virus being detected in Asia that may spark the next human outbreak, the World Health Organization said.

New variants of the H5N1 avian flu virus have emerged as the disease spread in birds across Asia to Europe and Africa during the past year, the WHO said last week. A pandemic based on one of these variants may not be protected by prototype vaccines being developed by about 30 companies worldwide. Most use a pilot vaccine derived from Vietnam about two years ago.

Three new pilot vaccines that may provide better protection against the dominant H5N1 strains have been identified, the WHO said. Studies are under way to test whether a vaccine that protects against one variant will be effective against another.

``It is a good idea to make strains available for each antigenic variant of the virus,'' said Ron Fouchier, a virologist at the Erasmus University in Rotterdam.

The human death toll from H5N1 has tripled this year as the virus spread in wild birds and domestic poultry to at least 38 countries. Since 2003, H5N1 is known to have infected 239 people in 10 countries, killing 140 of them, the WHO said on Aug. 17.

Officials at the Geneva-based health agency say that the world is now closer to another influenza pandemic than at any time since 1968, when the last of the previous century's three major outbreaks occurred.

London-based GlaxoSmithKline Plc, Paris-based Sanofi-Aventis SA and Novartis AG's Chiron unit are among companies working on pre-pandemic vaccines.

Shots produced each year for seasonal flu won't be effective in a pandemic because the vaccine needs to closely match the pandemic virus, according to the WHO. No pandemic shot is expected to be widely available until several months after the start of a worldwide outbreak, it said.

$2 Trillion Cost

A flu outbreak killing 70 million people worldwide may cause global economic losses of as much as $2 trillion, Milan Brahmbhatt, a World Bank lead adviser in the East Asia region, said in June.

The initial pilot vaccine represented a family, or clade, of H5N1 viruses circulating in Cambodia, Thailand and Vietnam which caused human infections in those countries during 2004 and 2005, the WHO said.

A second H5N1 clade circulated in birds in China and Indonesia during 2003-2004, and subsequently during 2005-2006, spread westwards to the Middle East, Europe and Africa, the agency said. This group of viruses, which share a common genetic makeup, has been principally responsible for human cases since last 2005, the WHO said.

Geographical Spread

Strains from this second clade can be further distinguished into six subclades, of which three additional pilot vaccines have been prepared, the agency said. National authorities may recommend the use of one or more of these new pilot vaccines, which were selected on the basis of the geographical spread, the epidemiology, and the antigenic and genetic properties of the H5N1 viruses isolated from humans during the past year.

The new pilot vaccines are based on a 2005 virus strain from Indonesia that resembles one found in a bar-headed goose from China's northwest province of Qinghai last year, and a virus similar to that collected in the country's southeastern province of Anhui in 2005.

``Since we do not know which lineage may cause a pandemic, multiple strains are selected by the WHO network which, together with the strains that have been selected previously, should cover the entire spectrum of antigenic variants that are circulating,'' Fouchier said.

To contact the reporter on this story: Jason Gale in Singapore at j.gale@bloomberg.net

Last Updated: August 21, 2006 01:33 EDT