Navigation Links
New details on how the immune system recognizes influenza

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 bioterroris t 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.

In addition, 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 recognized by a type of immune cell known as a T cell; far fewer are recognized by B cells, a type of white blood cell that produces infection-fighting antibodies. Antibodies induced by seasonal and pandemic flu viruses or vaccines are a major component of immunity that protects against these viruses.

Strains of influenza virus can vary enough in their neutralizing 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.

U sing 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.

Other analyses revealed major gaps in scientists' knowledge about influenza viruses. Of the 600 epitopes in the database, for instance, very few were from strains of H5N1 avian influenza. And even though the database contains epitopes from all the influenza virus' proteins, the vast majority of the data relates to just two influenza proteins, the hemagglutinin (HA) and nucleoprotein (NP).

Most of the influenza virus data comes from analyses of immune responses obtained with mice; some comes from rabbits, ferrets and monkeys, and very little comes from humans or birds. In fact, only one antibody epitope came from a human. The LIAI researchers say more studies should be focused on identifying human T and B cell epitopes from human and avian strains of influenza virus--especially those associated with protective immunity.

"The bottom line is that this study shows us where we need to go," says project director Stephen Wilson, Ph.D., chief technology officer at LIAI. "Hundreds of flu epitopes have already been published and are now in the database, but critical gaps become apparent when one looks for human antibody targets."

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 numerous tools for analyzing and visualizing the data and for predicting immunity against different pathogens--all of which is publicly access ible on their Web site (see http://immuneepitope.org).


'"/>

Source:NIH/National Institute of Allergy and Infectious Diseases


Related biology news :

1. Nonlinear Dynamics announces more details of its global partnership with PerkinElmer
2. Researcher uncovers details of how cancer spreads
3. Research details how a virus hijacks cell signals to cause infection
4. Study reveals details of mussels tenacious bonds
5. Study details hepatitis C ability to block immune system response
6. Researchers discover new details about HIV-1 entry and infection
7. Fox Chase Cancer Center scientists identify immune-system mutation
8. Genetically modified natural killer immune cells attack, kill leukemia cells
9. Studies reveal methods viruses use to sidestep immune system
10. Jumping gene helps explain immune systems abilities
11. Scientists solve structure of key protein in innate immune response
Post Your Comments:
*Name:
*Comment:
*Email:


(Date:6/21/2016)... June 21, 2016 NuData Security announced today ... role of principal product architect and that ... of customer development. Both will report directly to ... The moves reflect NuData,s strategic growth in its ... high customer demand and customer focus values. ...
(Date:6/16/2016)... 16, 2016 The global ... to reach USD 1.83 billion by 2024, according ... Inc. Technological proliferation and increasing demand in commercial ... to drive the market growth.      ... The development of advanced multimodal techniques for biometric ...
(Date:6/9/2016)...  Perkotek an innovation leader in attendance control systems is proud to announce the ... employers to make sure the right employees are actually signing in, and to even ... ... ... ...
Breaking Biology News(10 mins):
(Date:6/24/2016)... ... June 24, 2016 , ... While the majority of commercial ... Cary 5000 and the 6000i models are higher end machines that use the more ... the spectrophotometer’s light beam from the bottom of the cuvette holder. , FireflySci ...
(Date:6/23/2016)... June 23, 2016   Boston Biomedical , ... compounds designed to target cancer stemness pathways, announced ... granted Orphan Drug Designation from the U.S. Food ... gastric cancer, including gastroesophageal junction (GEJ) cancer. Napabucasin ... to inhibit cancer stemness pathways by targeting STAT3, ...
(Date:6/23/2016)... ... 23, 2016 , ... Charm Sciences, Inc. is pleased to ... AOAC Research Institute approval 061601. , “This is another AOAC-RI approval of the ... Vice President of Regulatory and Industrial Affairs. “The Peel Plate methods perform comparably ...
(Date:6/23/2016)... ... 23, 2016 , ... Supplyframe, the Industry Network for electronics ... Lab . Located in Pasadena, Calif., the Design Lab’s mission is to bring ... designed, built and brought to market. , The Design Lab is Supplyframe’s physical ...
Breaking Biology Technology: