Molecular detail on influenza epitopes

A comprehensive analysis of influenza A epitopes, the critical sites on the virus that are recognised by the immune system, has been published by researchers from California's La Jolla Institute for Allergy and Immunology (LIAI).

Published online 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.

The analysis drew upon LIAI's Immune Epitope Database and Analysis Resources Program, a single repository of immune epitopes from critical disease-causing microbes.

Lead investigator Dr Allessandro Sette, who heads the vaccine discovery division at LIAI, 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 epitopes are between different strains of bird and human influenza viruses.

Only a handful of the epitopes are known to be associated with protective immunity. Most of the influenza virus epitopes in the database are those recognised by T cells, but far fewer are recognised by B cells. Strains of influenza virus can vary enough in their neutralising B cell epitopes that a vaccine against one strain may not protect against another strain. But if epitopes are conserved between virus strains, the immunity a person has developed towards one strain might provide at least some protection against the other strain.

Using a software tool they developed, the LIAI team found hundreds of conserved influenza virus epitopes in the database, including those between avian H5N1 and strains of human influenza viruses. But what is less clear from the analysis is how cross-reactive an immune response would be to most of these conserved epitopes. Further analyses may assist scientists in identifying vaccine targets that might offer broader protection and in predicting how effective a new vaccine will be.

Plans for the future include adding data on epitopes that are involved in autoimmune diseases and epitopes that trigger allergic and asthmatic reactions. Dr Sette and his colleagues have also built tools for analysing and visualising the data and for predicting immunity against different pathogens, all of which is publicly accessible on their website at www.immuneepitope.org