A Wadsworth Center Study Sheds Light on the Evolution of Influenza Virus and the Impact on Vaccine, Disease

ALBANY, NY October 20, 2005 - An explanation for the diminished effectiveness of the 2003-04 flu vaccine was revealed in an analysis of influenza virus specimens collected in New York state over the last five years. The study also showed for the first time that several distinct strains of influenza virus circulated within a given flu season.

Scientists from the Department's Wadsworth Center and their collaborators used stored virus cultures from 1999-2004 in the first ever large-scale sequencing of the influenza genome. Their findings appear in this week's issue of the international journal Nature, and were published online earlier.

The researchers discovered that while the H3N2 influenza predominated during the last five years, three distinct subpopulations, or genetic variants, were found that sometimes circulated simultaneously.

They also found why the 2003-04 flu vaccine provided only partial protection. New influenza strains emerge when viruses mutate or swap genetic material as they move through their human hosts. Vaccines are produced based on the best prediction of which strains from an earlier season will return the following year. Late in the 2002-03 season, the predominant strain swapped genetic material with another minor variant, an event unanticipated by vaccine designers.

"The findings of the new study remind us that scientists here and around the world work diligently throughout the year to uncover clues that can help improve influenza treatment and prevention," said State Health Commissioner Antonia C. Novello, M.D., M.P.H., Dr.P.H. "The Wadsworth Center's dedicated efforts and collaboration with scientists across the globe have resulted in discoveries that will help better prepare our public health response to influenza in the future."

The study's authors include Jill Taylor, Ph.D., and Kirsten St. George, Ph.D., from Wadsworth's Virus Reference and Surveillance Laboratory, which performs diagnostic and reference testing for influenza and other respiratory viruses. They are participants in the Influenza Genome Sequencing Project, a joint effort with the National Institutes of Health and The Institute for Genomic Research to reveal the genetic blueprint of human and avian influenzas by fully sequencing thousands of influenza strains.

Influenza sequences available until now focused primarily on two genes that code for key surface proteins, hemagglutinin (H) and neuraminidase (N). This new genome-wide effort sequenced all eight viral genomic fragments, in the process determining the order of more than 2.8 million nucleotide bases, the virus' genetic building blocks. Mining these genomic data yielded several surprises.

By selecting "garden variety" influenza isolates, rather than those associated with virulent disease, for example, and choosing specimens from across the state and age groups, the Wadsworth scientists ensured an unbiased view of the virus as it moved through the human population. This snapshot of influenza evolution will benefit drug discovery and vaccine design, and enhance the ability to respond to a pandemic.

All 209 influenza sequences have been deposited in GenBank®, a public database accessible to scientists worldwide. Since the Nature paper was submitted, an additional 200 full sequences have been deposited.

"Wadsworth's rich repository of influenza isolates owes its existence to visionary scientists who began archiving specimens in the 1940s. As today's researchers, health practitioners and the community at large become more concerned about an influenza pandemic, we are pleased to have shared this resource in a way that helps advance influenza science," said Dr. Taylor, Wadsworth's lead on the project.

In the project's next phase, Wadsworth scientists will continue to choose isolates for sequencing. Capitalizing on relationships with virologists in their native Australia, Drs. Taylor and St. George are collecting influenza isolates from Australian health departments and hospitals. This will allow comparison of influenza strains circulating in the study's equivalent time period in another geographically distant site.

They also will select for sequencing historic examples that are among the some 2000 isolates held in -80 c. freezers at Wadsworth. Many of the original patient specimens from which the viruses were isolated and grown are also available, a value-added aspect that allows Wadsworth scientists to apply emerging technologies and new testing methods they develop to unearth additional information from specimens.