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Harmless virus may aid in knocking out deadly bird flu.

Use of a harmless virus as a delivery vehicle may help set a roadblock to a potentially catastrophic human outbreak of bird flu, according to researchers at Purdue University and the Centers for Disease Control and Prevention (CDC). The researchers are Purdue molecular virologist Suresh Mittal; Harm HogenEsch, co-principal investigator and head of Purdue's Department of Veterinary Pathobiology; and Jacqueline Katz and Suryaprakash Sambhara, both co-investigators from CDC. Under a $1.6 million grant from the National Institute of Allergy and Infectious Diseases (NIAID), they are investigating a new way of providing immunity against avian influenza viruses, the most lethal of which, H5N1, has a 50 percent fatality rate in humans.

"The ultimate goal of our research is to develop an effective avian influenza virus vaccine that will provide long-lasting and broad immunity against multiple strains," Mittal said.

Current vaccines are designed for strains of flu found in local areas and are effective only as long as the virus doesn't change form. Existing vaccines will have limited success against new strains of avian influenza. Every time a bird flu mutates, vaccines must be redesigned.

An additional important advantage to using an adenovirus as a vector of vaccine into cells is that it could be mass produced much more quickly than current vaccines. The proteins that form the basis for all of today's flu vaccines are grown in fertilized chicken eggs. It takes months to produce a new vaccine for a new virus strain by this method. Keeping pace with virus mutations can be difficult.

"Do we still want to depend on the egg to make our flu vaccines?" Mittal said. "When these types of viruses strike humans, they also strike poultry. In that case, the availability of fertilized eggs to make enough vaccine will be compromised."

It would be difficult to rapidly produce enough protective medication to stem a pandemic, according to experts from CDC, World Health Organization, and NIAID. But a large quantity of an adenovirus-based vaccine could easily be produced on short notice, according to Mittal.

"We already know how to grow large amounts of adenovirus and how to purify it, because adenoviruses already are used in clinical trials for gene therapy as vectors," he said.

A "medium-level" bird flu pandemic in the United States would kill between 90,000 and 200,000 people, and another 20 million to 47 million would be sickened, CDC experts estimate. The economic impact on the United States alone would be between $71.3 billion and $166.5 billion.

Since 2003 about 60 people have died in Southeast Asia from H5N1. Millions of poultry have died or been euthanized. Outbreaks in birds have been confirmed in 11 countries, and the disease is spreading north into countries outside of Southeast Asia; it has already been reported in Russia. No cases of this type of bird flu have been found in the United states, but CDC has reported two human cases of another type of bird flu in the United States in recent years--H7N2 in Virginia in 2002 and New York in November 2003.

Viruses are classified according to the combination of two types of proteins found on the virus cell surface. The 15 types of hemagglutinin (H) protein and nine types of neuraminidase (N) protein form a large number of influenza viruses for which birds are the natural hosts. New, often more dangerous, flu strains develop when the H and N combinations change. The virus alterations work a bit like a jigsaw puzzle: As two viruses grow in the same animal, they replicate and reassemble their genome. If one virus takes a piece of genome from the other virus to fill an empty spot, a new virus is born. When the genes of a human or swine influenza mix with an avian variety, a highly pathogenic human flu likely will result, Mittal said.

The potential for a pandemic exists when one of these new viruses is introduced into the human population. People with no previous exposure to the new flu strain have little or no immunity, making them highly susceptible to a virus that now can easily spread from person to person.

The last pandemic occurred in 1968-1969 when 34,000 Americans died of the Hong Kong flu (H3N2), a disease that is still circulating. In 1957-1958, Asian flu (H2N2) killed 70,000 people in the United States. The worst flu pandemic was in 1918-1919, when Spanish flu (H1N1) was fatal to 500,000 people in the United States and as many as 50 million worldwide. Unlike in other influenza outbreaks, the origin of that virus is still unknown.

Scientists believe that without the right vaccines and preparation, H5N1 has the potential to be one of the deadliest flu outbreaks if it mutates to a form that is easily transmitted between humans.
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Title Annotation:EH Update
Publication:Journal of Environmental Health
Geographic Code:1USA
Date:Dec 1, 2005
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