New flu vaccine from Penn shows promise

University of Pennsylvania researchers have genetically engineered a vaccine that completely protected mice and ferrets from deadly influenza viruses, including the infamous 1918 strain that killed 40 million people worldwide.

If the vaccine works in humans - a big if, experts say - it could be a platform for a so-called universal flu vaccine, effective in virtually all people against all flu strains. Such a vaccine could be stockpiled as a defense against an emerging flu pandemic or even used to protect particularly vulnerable groups from seasonal influenza.

"We congratulate the researchers on what is clearly a new and novel approach," said epidemiologist Michael Osterholm, an internationally known biosecurity expert at the University of Minnesota. "This is one of those stay-tuned efforts that surely could be very important."

Penn gene-therapy researcher James M. Wilson, leader of the study, said development of the approach "has taken on more urgency" in light of the outbreak of a virulent new bird flu strain in China. Like the 2004 bird flu that spread throughout Asia, the latest one is not easily contracted or transmitted by humans, but that could change with the ever-mutating virus.

The study, published Wednesday in Science Translational Medicine, involved using gene-transfer technology to make cells in the nose - where flu virus enters - that produce a powerful infection-fighting molecule called a "broadly neutralizing antibody."

This antibody was discovered two years ago by a team of British and Swiss researchers. It is the only antibody known to target the flu's Achilles' heel - a protein found on the surface of all 16 subtypes of the most dangerous influenza.

This flu protein, which the virus needs to break into cells, normally manages to sneak by the immune system. The vaccine overcame this problem by turning cells in the animals' noses into sentries that kill the virus.

The animal tests were conducted in Canadian government labs that maintain a high-security storage facility of many of the world's most fearsome infectious agents. Both the mice and the ferrets survived lethal doses of the 1918 "Spanish" flu and more recent pandemic strains.

"We were quite surprised to see" the effectiveness of the vaccine, said study coauthor Gary Kobinger, chief of special pathogens with the Public Health Agency of Canada in Winnipeg. "It's rare that we test something that works against the 1918 flu strain."

Conventional seasonal flu vaccines are still produced using antiquated 1940s technology: chicken eggs. The process takes months, requires guesswork about what strains will be circulating, and results in a marginally effective product. In adults over 65, it barely protects at all, studies show.

However, conventional vaccines endow the immune system with a permanent memory of an infectious invader. The new one does not. It works only until the genetically rigged nose cells die during natural cell turnover, not long enough to outlast a pandemic. Wilson believes this is a good thing.

"What we have to worry about is safety," he said. "If it lasted forever and caused irritation, that's a problem. This way, we can readminister it as needed."

Wilson also believes this vaccine approach could "hit the clinic quickly" because the gene is transported into nose cells by a deactivated virus, called a vector, that his lab discovered and has safely used in humans.

Wilson has focused on finding and distributing safe, efficient vectors ever since a study he led caused the 1999 death of Arizona teenager Jesse Gelsinger - the world's first gene-therapy victim. (Wilson has apologized for his role in the case and has disclosed his financial interests in the new vector and vaccine technology.)

Other experts said the idea of giving a genetic therapy over and over raises unprecedented testing and regulatory issues. And as history has shown, the flu uses humans and animals as genetic cauldrons, endlessly mutating to evade their defenses.

"We don't know what effects the widespread use of this vaccine might have on influenza virus evolution," said Thomas Friedrich, a flu researcher at the University of Wisconsin in Madison. "It might be difficult for viruses to mutate to avoid detection by this particular antibody, but if they did, they would render the vaccine useless."

"There is still a lot to do before someone can scream 'victory,' " acknowledged Kobinger, in Winnepeg. "But this is definitely one of the most exciting strategies we have tested."

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