Research on avian flu vaccine takes priority

Washington -- It's very good news that there is a vaccine that seems to offer protection from the deadly H5N1 virus that is infecting people in Asia and being carried westward, apparently by migrating birds.

However, whether the vaccine will be effective against a strain of the virus that can be easily passed from person to person is the great unknown that has kept researchers hard at work. Another big unknown: how to produce a vaccine fast enough and in sufficient quantities to protect everyone.

The Dept. of Health and Human Services estimates that as many as 1.9 million deaths could occur in the United States alone in the first 12 to 24 months of a lethal bird flu outbreak.

Michael Osterholm, PhD, MPH, director of the University of Minnesota's Center for Infectious Disease Research and Policy, has been involved with several of the most frightening public health battles of the past 30 years -- think HIV/AIDS, SARS and antibiotic resistance. But he was always able to sleep at night. "Now I lie awake thinking about pandemic flu," he said during a news briefing last month on global health risks. "We can't ignore the giant dinosaur in our kitchen."

Researchers who are on the trail of an effective pandemic flu vaccine, as well as faster methods to develop and manufacture one, aren't ignoring that dinosaur, but are circling it warily.

Promising results have emerged from a trial sponsored by the National Institute of Allergy and Infectious Diseases regarding an H5N1 flu vaccine under investigation.

The trial was conducted at three sites with about 450 healthy adults ages 18 to 64 who were injected with two doses of the newly developed vaccine a month apart, or with two doses of a placebo.

Vaccine doses tested were 7.5 μg, 15 μg, 45 μg and 90 μg, said James Campbell, MD, assistant professor of pediatrics at the University of Maryland School of Medicine and a lead investigator on the trial.

In comparison, the annual flu vaccine generally contains 45 μg of virus, a mixture of the three circulating strains identified in a given season.

Preliminary results show that two inoculations of 45 μg or 90 μg each elicited immune responses that would likely ward off infection by a lethal flu, said Dr. Campbell. However, a single shot of vaccine, at any dose, yielded very little immune response.

The vaccine was found to be generally safe and well-tolerated, said John Treanor, MD, professor of medicine at the University of Rochester, N.Y., and another investigator on the trial. The researchers expect to publish their findings shortly.

Sanofi Pasteur in Swiftwater, Pa., manufactured the trial vaccine, which is an inactivated vaccine made from the H5N1 virus isolated in Southeast Asia in 2004.

HHS has purchased enough doses of the vaccine for 20 million people and has contracted for additional vaccine.

Scrambling the eggs

The vaccine will be grown in eggs, a time-tested technique, but one that is also very time-consuming, requiring about six months and hundreds of millions of eggs to produce a supply sufficient for the U.S. population.

Manufacturers, including Sanofi and Chiron, are also working toward an eggless future in which the virus is grown not in eggs but in special cells, which can include human, dog or even insect cells.

Although this process has yet to be licensed in the United States, it has been approved in Europe.

A major benefit of cell culture is speed, likely shaving a few weeks from the startup process in vaccine development, said Len Lavenda, a Sanofi spokesman.

"It would allow very rapid vaccine production and it would even allow us to grow cells, freeze them and store them," said Greg Poland, MD, who heads the Mayo Clinic College of Medicine's Vaccine Research Group. "That's a very promising technology and, I would say, a proven one."

However, since vaccine production cannot get underway in earnest until the pandemic virus emerges and is replicated in the lab, sufficient quantities of the most effective vaccine would still be several months away.

Intending to get a head start on an emerging pandemic strain, NIAID is also working with MedImmune, a Maryland-based manufacturer of the live, attenuated vaccine already available for annual flu protection, to develop vaccines for all of the potential strains, including H5N1.

"The program is designed to develop the expertise and information base on how to make these vaccines and how they behave in people," said Kanta Subbarao, MD, MPH, senior investigator at NIAID and a lead investigator in the effort. "Are they safe? Are they immunogenic? And would they be an option? It is definitely a research development effort at this point."

In another effort, Huaguang Lu, DVM, senior research associate in the Dept. of Veterinary and Biomedical Sciences at Penn State in University Park, recently announced that he and his colleagues have developed a novel rapid diagnostic test that can detect all subtypes of avian virus, including H5N1, in just a few hours, compared with three to 10 days.

There are several other approaches to vaccine development that are also being explored. Among them is a DNA-based vaccine that could be produced quickly and in large quantities. It would be administered by propelling it into the skin, eliminating the need for needles.

"I think it's important that we look down each of those avenues and hope that at least one of them or multiple ones turn out to be ways to prevent pandemic flu," said Dr. Campbell.

It would be a mistake, said several researchers, "To put all of our eggs in one basket."