Bird Flu Vaccine Shows Promise in Mid-Stage Trials

For over a decade, scientists have been searching for an effective human vaccine against the H5N1 avian virus, commonly known as bird flu. Last year, the U.S. Food and Drug Administration approved the first such vaccine, which at the time was considered an "interim measure" in case of an epidemic. But on June 11 scientists released trial results on a new vaccine developed using monkey cells grown in labs. The new vaccine appears to be not only safe and more effective than its predecessor, but it can also be manufactured more quickly, which is a vital quality in case of an epidemic.

The vaccine, called Celvapan, is manufactured by Baxter International, Inc. It is grown directly in cell cultures and can be produced in large vats, reducing processing time to about 12 weeks, compared with 22 weeks with current vaccines that are grown in fertilized hens' eggs. Not only does this process allow the vaccine to be stockpiled quicker, but also offers a way to make seasonal flu vaccines much faster, giving health officials added time to match the shot to the flu strains circulating. In addition, the vaccine did not require an adjuvant, a substance added to a vaccine to boost its strength.

Mid-stage testing involving 275 adults in Austria and Singapore showed two doses of the vaccine produced an immune response strong enough to protect 76 percent of healthy adults from the Vietnam H5N1 strain and the related Hong Kong strain, compared with only 45 percent protection of the currently approved vaccine. It also appears to protect 45 percent from the Indonesia strain. The most common reaction was pain at the injection site, and the most common side effects experienced were headaches, fatigue, and injection site reactions.

According to Dr. Hartmut Ehrlich, the study's lead author and head of research and development for Baxter's Bioscience unit, the same dosage also proved effective in final-stage testing last year in Austria and Germany. It protected 73 percent of the 550 volunteers under the age of 60 and 74 percent over 60 from the Vietnam strain, but was less effective against the Indonesian one. It wasn't tested against the older Hong Kong strain. In the United States, the U.S. National Institute of Allergy and Infectious Diseases (NIAID) is also conducting a trial with Celvapan.

But despite impressive trial results, some experts remain cautious. Dr. Pascal James Imperato, dean of the graduate program in public health at the State University of New York (SUNY) points out that since the vaccine was only tested in younger adults, it is unclear how older adults would respond. "We know that younger adults tend to form antibodies to influenza vaccines much better than older adults," he said. Dr. Imperato also feels that multiple doses are a drawback. "As soon as you have to give two doses of a vaccine, even if it's not at a very long interval, it presents a problem with public compliance."

Still others believe it is unlikely that bird flu will pose a major threat to humans. Dr. Marc Siegel, an associate professor of medicine at New York University School of Medicine, and author of Bird Flu: Everything You Need to Know About the Next Pandemic, said, "I still think there's no reason to believe that a virus that's so pathogenic to birds is automatically going to become pathogenic to humans. In fact, most pandemics come from low-pathogenic viruses." Dr. Siegel does admit that, because of the high mortality rate, we should watch the virus carefully, but says "that doesn't mean by any stretch of imagination that it's going to become a human virus."

At least 16 other pharmaceutical companies are working on human vaccines against H5N1, some using cells or genetic engineering but the majority made from eggs. However, Baxter says theirs is the first produced in cells that's been tested in people. Earlier this year, Celvapan was submitted to the European Medicines Agency (EMEA) for licensure review. Officials at Baxter say they expect to receive approval from the European Union around year's end.

According to the study, Baxter has delivered several million doses of the vaccine to various governments around the world. As part of an agreement announced in February 2006, the company delivered a stockpile of two million doses to the U.K. Department of Health. Also in 2006, Baxter entered into a pandemic preparedness contract with the Austrian Ministry of Health to supply 16 million doses of the vaccine in the event a pandemic is declared.

In an article accompanying the study, Peter Wright, a professor of pediatrics at Dartmouth College in Hanover, New Hampshire, said an experimental vaccine produced using monkey cells begins to address some of the problems with the current stockpiles of avian flu vaccine. Global health officials are reportedly concerned that the millions of doses that have been stockpiled for years could be losing their potency and are calling for adjuvants to be set aside to strengthen them.

Last week, 120 influenza and planning experts from World Health Organization (WHO) Member States, research institutions and United Nations agencies around the world met in Geneva to review the current WHO pandemic preparedness guidance, first provided in 1999 and last revised in 2005. "New concepts and tools including the International Health Regulations 2005, the global pandemic influenza action plan, antiviral and H5N1 vaccine stockpiles, pandemic severity scale and a rapid containment protocol have emerged since the last revision," said Dr. Keiji Fukuda, Coordinator of the WHO Global Influenza Program. "Experience gained through dealing with H5N1 outbreaks, and through active preparedness by many countries makes this review a crucial exercise." WHO will release the revised guidance later this year.

Both the study and Professor Wright's companion paper were published in the June 12 issue of the New England Journal of Medicine.