Ever-changing flu outwits scientists searching for vaccine

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Lifelong vaccines protect against polio, smallpox and rubella, which begs the question of why a long-lasting universal vaccine has yet to exist for influenza.

The quick answer: Influenza is one clever family of viruses. But researchers continue making progress in developing a more comprehensive, long-lasting vaccine, which the National Institutes of Health has set as a national health care priority.

Influenza is the viral version of Jesse James -- dangerous, often deadly and elusive. Multiple versions of the virus exist, each with an evolutionary knack for disguising itself so it can slip past the immune system's security detail.

The NIH's National Institute of Allergy and Infectious Diseases lists about eight researchers, including a former University of Pittsburgh professor, who are focused on developing a new flu vaccine. But human clinical trials aren't likely for another five years, which pushes public availability of a universal vaccine to a decade or longer.

"You can't rush science," said Anthony S. Fauci, director of the allergy institute. "The universal flu vaccine is a very important goal. There's been some proof of concept over the past couple years with modest success, but it is not yet ready for prime time."

This year's flu season in Allegheny County exemplifies the challenge of formulating a successful flu vaccine in spring and summer months based on which A and B flu strains are predicted to circulate in the fall.

This year's flu vaccine correctly predicted the A and B strains, with the A strain causing 90 percent of the confirmed cases in Allegheny County. In late February, the B strain represented up to 50 percent of new cases. So far this year, the flu led to 14 deaths of people in ages ranging from 53 to 98.

In one troubling trend this year, some who received the vaccine contracted the flu, albeit typically less severe cases, said Ronald Voorhees, Allegheny County Health Department interim director. That occurs, he said, when flu strains, even those included in the vaccine, undergo changes during the season, diminishing the vaccine's effectiveness.

Health department surveillance, based on what percentage of people entering emergency rooms had flu symptoms, almost have fallen to baseline, indicating the season is in its final throes. But the season was more severe than recent years, particularly for those 65 and older, the CDC said. It doesn't provide an annual flu death toll but estimates about 36,000 average deaths a year. This year's flu season exceeded epidemic levels.

"This season is an example of the serious public health toll that influenza can take, and underscores the importance of influenza vaccination and treatment," the CDC states. "Influenza activity in the United States began to increase in mid-November and remained elevated through Feb. 9, 2013."

How the flu virus disguises itself involves the hemagglutinin (HA) protein on its surface, which typically should activate the immune system. An antigen is a foreign protein or substance that causes the immune system to produce antibodies against it.

Consider the antigen to be a dangerous terrorist and the antibody serving as the drone determined to destroy that type of terrorist. But the flu virus avoids an attack because the surface antigen changes, disguising itself so the immune system can't recognize it. That's likely what occurred during the flu season, leading to infections in people who received the vaccine.

For that reason, vaccine research has shifted to identifying an unchanging segment of the antigen protein, which turns out to be the protein stem.

"The stem is physically and structurally much more hidden from the immune system than the head that stands out," Dr. Fauci said. "When the vaccine exposes the stem part rather than the head, the immune system does make antibodies against the stem that's good against multiple strains of influenza."

Dr. Fauci said a recently departed Pitt professor is one of the cadre of researchers engaged in a promising pursuit of a universal flu vaccine.

"We still are using 1930s technology for the flu vaccines," said microbiologist Ted M. Ross, who left Pitt recently to serve as program director of the Vaccine & Gene Therapy Institute in Port St. Lucie, Fla. His vaccine already has been shown to prevent all A strains of flu in mouse studies, with his team now targeting B strains. "It's time to get a more modern vaccine," he said.

Each strain of the flu, isolated since 1930, has been shown to stimulate different sequences of DNA, causing an immune response tailored to that virus. The Ross vaccine is designed to go farther and stimulate a response to any and all sequences of the viral antigen -- overcoming its ability to disguise itself. That theoretically would produce a vaccine that protects against any known flu strain, including avian and swine flus.

The unanswered question for the Ross team is how its vaccine would continue working. Even a vaccine lasting several years and effective against multiple strains of flu would represent an improvement over current flu vaccines.

The former Pitt professor developed the A-strain vaccine at Pitt's Center for Vaccine Research, where he and the university formed a partnership with vaccine-maker Sanofi Pasteur, which will have an option for exclusive development and commercialization rights worldwide for any resulting flu vaccine the team produces.

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David Templeton: dtempleton@post-gazette.com or 412-263-1578.


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