seeking a universal vaccine

By John Lauerman

Dec. 11 (Bloomberg) -- Novartis AG and Sanofi-Aventis SA are among drugmakers searching for new weapons against influenza viruses that evade protection from existing vaccines.

Each year, a new strain of the flu virus circles the globe and kills as many as a half million people annually worldwide. As the virus changes annually into forms that can circumvent the human immune system, scientists are seeking the first universal vaccine against the flu.

To defeat the flu, doctors will need new vaccines with unprecedented power, said Albert Osterhaus, the head of virology at Erasmus University in Rotterdam. Such a vaccine should be able to protect against many strains at once, including the avian form arising in Asia that threatens to become a pandemic deadly to tens of millions of people.

``The real question is whether it's possible to do pre- pandemic vaccination or stockpile vaccine in advance of a pandemic,'' said Osterhaus, who helped organize a conference of flu experts gathering in Singapore this week to spur the quest.

The most recent flu pandemic, the 1968 Hong Kong flu, killed an estimated 34,000 people in the U.S. and at least a million worldwide. The 1918 Spanish flu, the largest flu wave on record, may have caused 50 million deaths globally. No one knows when the next pandemic will arrive or how devastating it will be.

Killer Virus

The five-day conference, ``Respiratory Viruses of Animals Causing Disease in Humans,'' which runs through Dec. 14, is timely because the H5N1 avian flu has killed 154 people since late 2003, according to the World Health Organization. The virus, contracted mostly from the blood or excrement of infected poultry, threatens to mutate into a version that can spread easily between people. Such a virus would be lethal to many because humans don't have immunity against it.

The H5N1 deaths have occurred in nine countries: Azerbaijan, Cambodia, China, Egypt, Indonesia, Iraq, Thailand, Turkey and Vietnam. A tenth, Djibouti, has had one confirmed human case, the WHO reports.

Vaccines are aimed at inducing immunity to disease. Much of the talk at the meeting is about chemicals, known as adjuvants, that boost the strength of existing types of vaccines.

``The most important question now is what is going to be the contribution of adjuvants to classical vaccines,'' Osterhaus said.

Master of Disguise

Novartis, based in Basel, Switzerland, uses an adjuvant called MF59 to beef up its Fluad vaccine. London-based GlaxoSmithKline Plc, Brussels-based Solvay SA, and Paris-based Sanofi Aventis also are experimenting with adjuvants.

While immune cells and proteins recognize and kill germs such as measles after a single confrontation, protection against the annually mutating flu must be given each year. The annual changes in the chemical structure of virus's eight genes can evade the human immune system's protective powers.

Almost a year before the U.S. flu season starts, germ trackers from the Geneva-based WHO and other public health groups begin sorting through viruses in Asia to find the three deemed most likely to move eastward and cause the next outbreak.

Sanofi, Glaxo, and Novartis take those strains, grow them in chickens' eggs, and then kill the virus to extract the proteins that go into vaccine shots.

``It's like choosing a boat to cross a continent,'' said Klaus Stoehr, a special adviser to the WHO, in a Dec. 5 interview in Boston. ``You hope one boat can get you across Niagara Falls and all the rivers.''

Mutations

It takes at least six months to go from the selection of viruses by WHO laboratories to makers' shipping vaccine. Meanwhile, the viruses that remain spreading may continue to change into forms that can evade the new shots.

About once every three years, the virus that hits the U.S. mutates enough from the one used to make the vaccine to reduce the effectiveness of the shots, said Stanley Plotkin, an adviser to Sanofi and an organizer of the conference. Once every decade the match between virus and vaccine is enough to drop effectiveness by 70 percent.

``We expect fabulous protection from vaccines,'' said William Schaffner, an infectious-disease expert at Vanderbilt University in Nashville, Tennessee, and a consultant to the U.S. government. ``Influenza vaccines are not there yet.''

The WHO has warned that vaccines stockpiled to fight the next pandemic may not work. If the H5N1 virus does mutate into a form that spreads quickly in people, that version may bear little or no resemblance to the strains spreading today or those used to make vaccines.

`Huge Difference'

Glaxo is trying to beat flu's elusiveness with adjuvant that has been shown to increase the power of a conventional flu shot, which contains parts of a killed virus, by about four times. Glaxo is developing the vaccine for multiple H5N1 types.

``The huge difference is that this is available now,'' said Emmanuel Hanon, head of Glaxo's worldwide flu franchise, in a Dec. 5 telephone interview. ``It will not take years to implement.''

Novartis, which acquired the MF59 adjuvant last year in its purchase of Chiron Corp., applied last month for a European license to use its H5N1 vaccine before a pandemic.

MedImmune's technology, which uses live, weakened flu virus, may offer advantages for immunization, WHO's Stoehr said. Whole virus grows quickly and provokes a strong immune response, he said, and the nasal-spray vaccine requires no needles to use.

`Broader Protection'

Baxter International Inc., based in Deerfield, Illinois, is developing a whole-virus vaccine against a pandemic flu, Stoehr said. Baxter is growing batches of virulent H5N1 virus taken from infected people and animals, the killing the virus and putting it into vaccine. Baxter published research in October showing the vaccine works in low doses, without an adjuvant.

Sanofi said it will ship 50 million doses of seasonal flu to the U.s., making it the country's largest supplier. Novartis will provide 30 million doses and Glaxo will sell 25 million. Medimmune, which sells a nasal version, said it will ship 3 million doses this year, almost double last year's amount.

All of the shots need to show that they can safeguard humans if used before a pandemic begins, said Osterhaus, the conference organizer.

``We need to know if they indeed fulfill the promise of broader protection against different H5N1 viruses,'' he said. ``We need hard data.''

To contact the reporter on this story: John Lauerman in Boston at jlauerman@bloomberg.net .