January 22, 2007

How the Immune System Recognizes Influenza

A young girl in bed with the flu

Scientists have completed the most comprehensive analysis to date of critical sites on the influenza A virus that are recognized by the immune system. The results should help scientists design new vaccines, diagnostics and therapies against both seasonal and pandemic flu.

The complete molecular structures of essentially all major strains of influenza viruses are already known. However, the body's immune response tends to concentrate on only limited regions of a virus. These immune target regions are called epitopes. Epitopes shared by different viruses are particularly important for the development of influenza vaccines because vaccines against them may provide protection against multiple strains.

Researchers at the La Jolla Institute for Allergy and Immunology (LIAI) turned to an effort called the Immune Epitope Database and Analysis Resources Program, which began in 2004 when NIH's National Institute of Allergy and Infectious Diseases (NIAID) awarded LIAI a contract to create a single repository of immune epitopes from critical disease-causing microbes, including agents that might be used in a bioterrorist attack. Dr. Alessandro Sette, who heads the Vaccine Discovery division at LIAI, and his colleagues examined 600 different epitopes from 58 different strains of influenza A virus.

The team published its findings on January 2, 2007, in the journal Proceedings of the National Academy of Sciences. They found hundreds of shared epitopes among different virus strains, including the avian H5N1 virus. However, only a handful of the epitopes are known to be associated with protective immunity. Most of the influenza virus epitopes in the database are recognized by a type of immune cell known as a T cell. Far fewer are recognized by B cells, a type of immune cell that produces infection-fighting antibodies, a major component of our immune protection against these viruses. Only one published epitope appears to be ideal for multi-strain vaccines.

"This study is interesting for what it shows we know and do not know," NIAID Director Dr. Anthony S. Fauci said. "It reveals many gaps in our knowledge of influenza viruses and indicates where we need to focus our attention."

How strongly the immune system would respond to most of these shared epitopes is still uncertain. In addition, almost all the data examined comes from animal studies; only one antibody epitope came from a human. Further research is needed to identify vaccine targets that can offer broad immune protection from human and avian strains of influenza virus.

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