Drawing upon a massive database established with funds from the National Institute of Allergy and Infectious Diseases (NIAID), one of the National Institutes of Health (NIH), scientists have completed the most comprehensive analysis to date of published influenza A virus epitopes--the critical sites on the virus that are recognized by the immune system. The findings, reported by researchers at the La Jolla Institute for Allergy and Immunology (LIAI), are being published online this week by the journal Proceedings of the National Academy of Sciences.

The study should help scientists who are designing new vaccines, diagnostics and immune-based therapies against seasonal and pandemic influenza because it reveals in molecular detail exactly where the immune system focuses on the viruses. Although the complete molecular structures of essentially all major strains of influenza viruses are known, immune responses concentrate on limited regions of certain parts of the virus, and these regions must be identified as immune epitopes by research studies. The LIAI team found that while there were hundreds of shared epitopes among different virus strains, including the avian H5N1 virus, only one has been published that appears ideal for multi-strain vaccines. Information on shared protective epitopes is important for developing influenza vaccines that can provide broad protection against multiple strains of the virus.

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

The analysis drew upon a much larger effort called the Immune Epitope Database and Analysis Resources Program, which began in 2004 after NIAID awarded LIAI a $25 million contract to create a single repository of immune epitopes from critical disease-causing microbes, including agents that might be used in a bioterrorist attack. Influenza epitopes comprise only a portion of the extensive database, which has become the largest single collection of such information anywhere in the world. It includes data from thousands of separate articles published over several decades, providing extensive dossiers on dozens of pathogens.

"The purpose of the database is to provide a catalog of molecules and structures that scientists around the world can quickly access and use to understand the immune response to a variety of epitopes, or methodically predict responses to as-yet untested targets," says Alessandro Sette, Ph.D., who heads the Vaccine Discovery division at LIAI and is the lead investigator on the project.

For the current study, Dr. Sette and his colleagues examined 600 different epitopes from 58 different strains of influenza A virus. One of their main goals was to determine how conserved, or similar, epitopes are between different strains of bird and human influenza viruses. Knowing this is important because the virus rapidly mutates and can swap gene segments between strains, which could increase the ability of an avian virus to be transmissible to humans.