Scientists develop vaccine against `Spanish flu' virus

Virulent strain killed millions

hopes rise for avian outbreak remedy

October 17, 2006|By Peter Gorner | Peter Gorner,CHICAGO TRIBUNE

Government scientists reported yesterday that they have created a vaccine against the catastrophic "Spanish flu" virus of 1918-1919, raising hopes that a remedy could be developed if a modern strain of avian flu turns equally deadly.

The Spanish flu, which infected a third of the world's population and caused as many as 100 million deaths worldwide, is unlikely to resurface. But interest in the epidemic has been revived over the past decade as experts gird for battle against an emerging bird flu they fear could mutate into a form able to pass from human to human.

Decoding the genes of a flu virus and developing a vaccine is now a matter of months, not years, said the lead researcher of the new report, Dr. Gary Nabel, director of the National Institute of Allergy and Infectious Diseases' Vaccine Research Center.

The study, published in the Proceedings of the National Academy of Sciences, "offers hope that conventional vaccination strategies will be an effective approach to a new pandemic influenza," said David Topham, an influenza immunologist at the University of Rochester Medical Center in New York who was not involved in the study.

No influenza virus has been nearly as virulent as the Spanish flu. In fact, many scientists of the time questioned whether such an explosively fatal disease could be influenza at all.

Later researchers hypothesized there was something about the virus that protected it from the actions of the immune system. If that was true, vaccines would not be effective against it.

Now, working with mice, scientists have shown that a vaccine can prompt the body's natural defenses to mount an attack on the virus, and that bodes well for future efforts to fight dangerous flu strains.

"The good news is that it's a bad virus but it's not resistant to vaccination," Nabel said.

The 1918 epidemic killed 675,000 people in this country, including 43,000 in the U.S. military and 8,500 in Chicago, doubling the normal death rate from all causes. The deadliest plague in human history, it was memorialized in literature - especially Katherine Anne Porter's Pale Horse, Pale Rider.

Its cause remains a mystery, though recent research suggests that the strain might have started as a bird flu before making genetic leaps that enabled it to infect humans.

Historic circumstances contributed to the 1918 pandemic, scientists note, including unprecedented movement by animals and people, military operations, overcrowding and poor sanitation.

But Dr. Jeffrey Taubenberger, a government researcher who used molecular techniques to reconstruct all eight genes of the Spanish flu virus, has suggested that even with today's medical advances, an equally virulent flu strain could kill 100 million people or more worldwide.

Experts have theorized that lack of prior exposure to the Spanish flu virus meant the immune system could offer no protection. That could explain why, unlike most flu strains, this one primarily attacked healthy young adults, causing raging fevers and delirium and drowning them in their own fluids.

A person could wake up healthy and be dead by nightfall. The main cause was viral pneumonia, and thus antibiotics, had they been invented, would have been useless. A vaccine, though, could have saved people.

It started to become clear that an influenza virus had caused the pandemic in the 1930s, when closely related influenza viruses were isolated first from pigs and then humans.

But the Spanish flu strain was not seen again until flu experts announced in 2001 that they had pieced it together from viral fragments preserved in samples from U.S. soldiers and by exhuming a female Inuit victim frozen in Arctic permafrost.

Then scientists set about trying to make a vaccine. The first step was to sequence all of the virus' genes, especially the hemagglutinin molecule - the "H" in the designation of any flu virus, including the potentially dangerous avian influenza virus H5N1. The molecule studs the outer surface of the virus and is the primary target of protective antibodies from the immune system.

Nabel and the research team made various forms of the hemagglutinin molecule in the Spanish flu virus and observed whether removing genetic material made it less virulent but still able to evoke an immune response.

Then they made weakened synthetic versions of the virus - one from the native 1918 virus and a second with mutated hemagglutinin. Both vaccines protected mice against infection.

The results demonstrated a "proof of concept" that immunization techniques are "likely to be successful for the generation of protective immunity in humans," the team wrote in their paper.

"Our findings also have relevance to people who are working with the virus," Nabel said. "We'll create small quantities of a prototype of this vaccine and keep it on hand in case it's ever needed."

Peter Gorner writes for the Chicago Tribune.

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