Penn Study Pinpoints New DNA Weapon Against Bird Flu

In the experiments, vaccinated macaques, mice and ferrets were protected from both disease and death when exposed to avian flu.

If proven in humans, this research could lead the way to effectively prepare against an outbreak of pandemic avian flu.

Health officials around the world worry that the H5N1 bird flu virus will mutate into a form that is readly transmitted from person to person, starting an influenza pandemic.

Patients hospitalized with avian influenza (Photo credit unknown)

In the latest bird flu outbreak which began in 2003, human cases of H5N1 bird flu have been documented in 15 countries. Data compiled by the World Health Organization shows 385 cases have occurred, and of these, 243 people have died.

The new vaccination method delivers the vaccine via synthetic DNA, or deoxyribonucleic acid, the hereditary material that contains the genetic instructions for the development and functioning of all known living beings.

Traditional vaccines expose a formulation of a specific strain of flu to the body so it can create immune responses against that specific strain.

But a DNA vaccine becomes part of the cell, giving it the blueprint it needs to build antigens that can induce responses targeting diverse strains of pandemic flu.

Because these synthetic DNA vaccines are effective against multiple cross strains, vaccines could be created and stockpiled, prior to a pandemic, and thus be delivered quickly in the event of an outbreak, say the researchers.

"This is the first study to show that a single DNA vaccine can induce protection against strains of pandemic flu in many animal models, including primates," says David Weiner, PhD, professor of pathology and laboratory medicine at the university.

"With this type of vaccine, we can generate a single construct of a pandemic flu vaccine that will give much broader protection," he said.

A duck is vaccinated against H5N1 avian flu. (Photo courtesy FAO)

Avian flu is tricky, Weiner said. Not only is it deadly, but it mutates quickly, generating different strains that escape an immune response targeted against one single strain.

Preparing effective vaccines for pandemic flu in advance with either live or killed viruses, which protect against only one or few cross-strains, is therefore very difficult.

How to predict which strain of avian flu may appear at any time is difficult. "We are always behind in creating a vaccine that can effectively protect against that specific strain," notes Weiner.

Influenza viruses are normally highly species-specific, meaning that viruses that infect an individual species - humans, certain species of birds, pigs, horses, and seals - stay “true” to that species, and only rarely spill over to cause infection in other species, according to the World Health Organization, WHO.

The one exception is the highly pathogenic H5N1 bird flu virus.

Health officials worry that the H5N1 virus - if given enough opportunities - will develop the characteristics it needs to start another influenza pandemic.

If proven in humans, the Penn research could lead the way to prepare against an outbreak of pandemic avian flu. (Photo courtesy U.S. Air Force)

"The virus has met all prerequisites for the start of a pandemic save one: an ability to spread efficiently and sustainably among humans," WHO states. "While H5N1 is presently the virus of greatest concern, the possibility that other avian influenza viruses, known to infect humans, might cause a pandemic cannot be ruled out."

To guard against this possibility, Penn researchers injected three different species of animals - macaques, mice and ferrets - with synthetic DNA vaccines that are not taken from the flu microbe, but trick the immune system into responding against pandemic flu.

Antibodies induced by the vaccine rapidly reached protective levels in all three animal species.

To ensure increased DNA delivery, the researchers administered the vaccine in combination with electroporation, a small, harmless electric charge that opens up cell pores facilitating increased entry of the DNA vaccine into cells.

"The synthetic DNA vaccines designed in this study customize the antigen to induce more broad immune responses against the pathogen," says Weiner. "DNA vaccines have the benefits and avoid many conceptual negatives of other types of traditional vaccines."

This research also has implications for non-avian types of flu. Every year, scientists try to guess what strain of the year will be that creates the common flu. Sometimes their educated guess is wrong, which is why last year's influenza vaccine worked only 30 percent of the time.

Weiner predicts that designing traditional vaccines in combination with the DNA platform may be a partial solution to this dilemma.

The Penn study was published last week in PLoS ONE. Dr. Weiner sits on the scientific advisory board of VGX, and collaborates with Wyeth, Merck, BMS, Althea, and Virxsys, as well as other companies on DNA vaccine technologies.

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