By Mary Powers
powers@gomemphis.com
April 9, 2003

A St. Jude Children's Research Hospital team has taken just weeks to develop an experimental vaccine against a deadly new flu virus, an accomplishment with a life-saving potential.

The almost round-the-clock effort, based on technology developed at St. Jude, raises hope for rapid development of vaccines - which now can take months or even years to develop - to protect against not just influenza but also other viruses. It was engineered against a deadly flu strain that surfaced just two months ago in Hong Kong.

It comes as public health officials worldwide scramble to understand and contain an outbreak of atypical pneumonia dubbed SARS, or severe acute respiratory syndrome. Although the exact cause of SARS is unknown, it has been linked not to the flu virus, but to a family of viruses that cause the common cold. Vaccine development cannot begin without a confirmed cause.

The St. Jude effort focused not on SARS but on the flu virus, long known for its ability to change and spread with rapid, deadly consequences. The 1918 flu epidemic, which killed at least 21 million worldwide, remains one of the worst infectious disease outbreaks in history. Public health officials have long warned that the world is overdue for another virulent flu virus.

St. Jude's candidate vaccine, the first developed against flu with a technology dubbed reverse genetics, has been sent to scientists in Hong Kong, the World Influenza Center in London and the federal Centers for Disease Control and Prevention (CDC) in Atlanta for further testing.

The vaccine's safety and effectiveness must still be demonstrated. Officials at the National Institutes of Health are in talks with several manufacturers about producing a sample batch of the vaccine as early as summer.

"Without the technology it might have taken months, if not years," to develop a candidate vaccine, said Dr. Linda Lambert of the National Institute of Allergy and Infectious Diseases (NIAID). She noted that researchers are still trying to develop a vaccine against a novel 1997 flu virus.

"The four-week time frame is just outstanding," said Lambert, who is NIAID influenza program director.

The St. Jude lab of Dr. Robert Webster is one of three under contract with the federal agency to generate viruses for possible vaccines.

St. Jude's announcement comes at time of heightened anxiety about natural and manufactured health threats.

The Bush administration's continuing war on terrorism and current war in Iraq have come with warnings that Americans at home and abroad are at increased risk of biologic attack.

Meanwhile, SARS has sickened more than 2,600 people worldwide and killed at least 104. U.S. health officials are investigating 148 suspect cases, none in Tennessee..

A flu virus sparked the St. Jude effort.

It surfaced in Hong Kong in February, killing a man and his 9-year-old son.

The virus came from the same family of viruses that appeared in Hong Kong in 1997, killing six. In response, health officials ordered the slaughter of more than 1 million chickens, ducks and other birds in the Hong Kong market.

It was an effort to wipe out the virus, which was apparently spreading from the domestic fowl to humans. The goal was to stop the virus before it acquired the ability to move from human to human.

Both the February 2003 and the 1997 viruses triggered international alarm because both are so different from other circulating human flu viruses and therefore more likely to cause death and disease. Both viruses first came to public attention in Hong Kong.

"We've had two warning shots. No one knows what will happen next," Lambert said.

Late last year wild migratory birds started dying in Hong Kong city parks. Then the human cases were diagnosed in February.

"It was no longer an option of getting rid of it by killing poultry," explained Webster, a St. Jude faculty member and director of the WHO's U.S. Collaborating Center. The center is based at St. Jude and focuses on how viruses jump from animals to humans.

WHO sent samples of this latest flu virus to Webster's St. Jude laboratory on Feb. 21. "We thought we could theoretically make the vaccine and we set a timeline to do it," Webster said.

By March 17, the group had developed the experimental vaccine.

"It was pretty much a day and night thing," said Dr. Richard Webby, who with Dr. Daniel Perez led the technical effort. "It was a bit strange to come to the lab at 4 a.m. and find you are the third person there."

Normally new flu vaccines are developed by mixing a virulent flu virus with a benign cousin. The nature of the flu virus means the two bugs will naturally shuffle their genes and give rise to new viruses. A researcher wades through all the new viruses that the technique generates to find one likely to trigger the desired immune response without causing illness.

It is time-consuming and results aren't guaranteed.

This time researchers directed the genetic shuffling using a technique called reverse genetics.

The technology was initially described by University of Wisconsin researchers in 1999. St. Jude researchers published an alternative system in 2000. In 2002, St. Jude scientists published a paper describing the use of the technology for vaccine development.

Along with knowing the cause of an illness, to develop a vaccine researchers must also know which parts of the virus trigger a protective immune response and which parts cause disease.

For this vaccine, they packaged the genetic material from two genes carrying instructions for making two proteins carried on the surface of February's deadly Hong Kong virus. They altered the biochemical composition of one to reduce its disease-causing ability.

Those proteins were included to prime the immune system so it would quickly recognize and overwhelm the actual virus.

For the remaining six genes, they turned to the benign flu virus that serves as the backbone of most flu vaccines.

The packaging technique allowed researchers to shuffle the genetic material like cassettes.

The goal was a new virus that would prime the immune system without causing sickness.

St. Jude researchers working on vaccines against croup and respiratory syncytial virus (RSV), a major problem in infants and young children, are now using the technology.

"It is an extraordinary new hope for (development of) viral vaccines. Before we've just dreamed of having this technology," said Dr. Elaine Tuomanen, director of St. Jude's infectious disease department.

"It is like having a vaccine emergency room."

- Mary Powers: 529-2383