The first experimental bird flu vaccine made from lab-grown cells instead of chicken eggs shows promise in blocking the highly lethal virus, scientists report.

The advance is good news not just for preparations in case of a pandemic, but also because it offers a way to make shots for seasonal flu much faster. That gives health officials crucial extra time to better match annual shots to the flu strains circulating.

It also would reduce dependence on the antiquated system of using millions of eggs to make flu vaccines and could cut production time roughly in half, to as little as 12 weeks, according to maker Baxter International Inc.

Results of mid-stage testing of the Baxter vaccine, Celvapan, showed two shots produced an immune response considered strong enough to protect 76 percent of healthy adults from both the H5N1 Vietnam strain it targets and the related Hong Kong strain; it appeared to protect 45 percent from a third, Indonesian strain.

"I think it is a big leap forward," said Dr. Wilbur Chen, a vaccine researcher at the University of Maryland School of Medicine not involved in the study.

Since the first outbreak in Hong Kong in 1997, more than 240 people in Asia, Europe and Africa have died from bird flu, which kills about two-thirds of people infected. Nearly all had close contact with poultry, but scientists worry bird flu could mutate to a form easily spread among people, who have no natural immunity. Many experts believe a pandemic will eventually occur.

On Wednesday, Hong Kong health officials ordered the slaughter of all live poultry in street markets due to one of the largest outbreaks of the virus in birds in years.

The United States has stockpiled 23 million doses of egg-based human bird flu vaccine made by three companies; some European countries also have such stockpiles and are ordering Baxter's cell-based vaccine.

Other human vaccines -- a few using cells or genetic engineering but most made from eggs -- are being tested in dozens of government and commercial projects. Baxter officials say theirs is the first produced in cells that's been tested in people, and they expect to get a European Union license for Celvapan around year's end.

The results of the company-funded study were reported in Thursday's New England Journal of Medicine.

Good results at low doses

A total of 275 volunteers in Austria and Singapore got one of four doses. The best results -- the 76 percent protection -- came from the second-lowest dose.

That dose also proved effective in a final-stage test last year of 550 volunteers in Austria and Germany, according to Dr. Harmut Ehrlich, head of research and development for Baxter's Vienna-based Bioscience unit. It protected 73 percent of adults under 60 and 74 percent of those over 60 from the Vietnam strain. It was less effective against the Indonesian strain and wasn't tested against the older Hong Kong one.

To measure effectiveness, volunteers' blood is tested to see how well the new antibodies they developed kill the virus.

Dr. William Schaffner, a Vanderbilt University infectious disease specialist, said researchers need to keep working to make a better vaccine but Baxter's got "pretty darn good results" at low doses.

"I'm excited about this, but we have not yet reached the finish line," he said.

In the United States, the Department of Health and Human Services has invested $1.5 billion in research on cell-based seasonal and pandemic flu vaccines.

In the half-century-old egg method, virus samples are injected into hundreds of millions of specialized eggs and incubated. The egg fluids are later harvested, concentrated and purified into the vaccine.

With cell technology, small amounts of virus are put in large fermenting tanks with nutrients and cells derived from monkey kidneys, and the virus multiplies. Then the virus is inactivated, purified and put into vaccine vials.

Two cell culture vaccines for seasonal flu are licensed in Europe, said Marie-Paule Kieny, director of the World Health Organization's vaccine research program. But full development of the technology could still take a few years, she said.

Experts said Baxter's vaccine appears to work better than egg-based ones, but cautioned that lab results from different companies are hard to compare.

Linda Lambert, chief of the respiratory diseases branch at the National Institute of Allergy and Infectious Diseases, said the Baxter vaccine's protection against multiple strains could be important if a pandemic is caused by a strain other than H5N1.

"If another pops up, we'll know what to do," based on what Baxter and other researchers have been learning, she said.

A Clinical Trial of a Whole-Virus H5N1 Vaccine Derived from Cell Culture

Hartmut J. Ehrlich, M.D., Markus M�ller, M.D., Helen M.L. Oh, M.D., Paul A. Tambyah, M.B., B.S., Christian Joukhadar, M.D., Emanuele Montomoli, Ph.D., Dale Fisher, F.R.A.C.P., Greg Berezuk, M.S., Sandor Fritsch, Ph.D., Alexandra L�w-Baselli, Ph.D., Nina Vartian, Ph.D., Roman Bobrovsky, Ph.D., Borislava G. Pavlova, Ph.D., Eva Maria P�llabauer, M.D., Otfried Kistner, Ph.D., P. Noel Barrett, Ph.D., for the Baxter H5N1 Pandemic Influenza Vaccine Clinical Study Team

Background: Widespread infections of avian species with avian influenza H5N1 virus and its limited spread to humans suggest that the virus has the potential to cause a human influenza pandemic. An urgent need exists for an H5N1 vaccine that is effective against divergent strains of H5N1 virus.

Methods: In a randomized, dose-escalation, phase 1 and 2 study involving six subgroups, we investigated the safety of an H5N1 whole-virus vaccine produced on Vero cell cultures and determined its ability to induce antibodies capable of neutralizing various H5N1 strains. In two visits 21 days apart, 275 volunteers between the ages of 18 and 45 years received two doses of vaccine that each contained 3.75 �g, 7.5 �g, 15 �g, or 30 �g of hemagglutinin antigen with alum adjuvant or 7.5 �g or 15 �g of hemagglutinin antigen without adjuvant. Serologic analysis was performed at baseline and on days 21 and 42.

Results: The vaccine induced a neutralizing immune response not only against the clade 1 (A/Vietnam/1203/2004) virus strain but also against the clade 2 and 3 strains. The use of adjuvants did not improve the antibody response. Maximum responses to the vaccine strain were obtained with formulations containing 7.5 �g and 15 �g of hemagglutinin antigen without adjuvant. Mild pain at the injection site (in 9 to 27% of subjects) and headache (in 6 to 31% of subjects) were the most common adverse events identified for all vaccine formulations.

Conclusions: A two-dose vaccine regimen of either 7.5 �g or 15 �g of hemagglutinin antigen without adjuvant induced neutralizing antibodies against diverse H5N1 virus strains in a high percentage of subjects, suggesting that this may be a useful H5N1 vaccine. (ClinicalTrials.gov number, NCT00349141 [ClinicalTrials.gov]