Feb 26 2009, 11:22 AM EST
GEN News Highlights
Scientists at Scripps Research and Crucell have found an immune system molecule that attacks what the investigators call the Achilles heel of a wide range of influenza viruses including those responsible for past global pandemics, those causing current common infections, and strains of bird flu expected to pose future problems.
So far, the researchers have shown the this molecule, called CR6261, works against many of the 16 different subtypes of influenza viruses. The antibody neutralized every H1 virus that the group tested, including those that have caused pandemics over the past 100 years. The antibody also worked on the H5 bird viruses that are not yet circulating in humans.
The CR6261 antibody, however, was not effective for the H3 subclass, which is a common human influenza virus, because a sugar molecule blocks the epitope. “If a sugar is the only impediment in the way, we think there is a way around that in vaccine design,” according to Ian Wilson, a professor in the department of molecular biology at Scripps Research.
The researchers extracted white blood cells from a healthy immunized volunteer to make a library of antibodies to look for antibodies that interact with viruses that the donor could not have come into contact with before, such as H5 avian influenza that has spread only from chickens to humans but not from humans to humans.
They found one such antibody, CR6261, in the blood of a donor who had recently been vaccinated with a flu shot to protect against H1 influenza virus. Crucell previously demonstrated in preclinical experiments that this antibody can neutralize common, seasonal flu viruses.
CR6261-like antibodies have now also been reportedly found in other people. It is likely that many people, if not all, have these antibodies, but the body doesn't always produce or use them efficiently, the investigators explain.
The researchers then tried to understand exactly how CR6261 recognized and responded to such a broad array of influenza viruses. To do that, the team solved two crystal structures: one with the antibody bound to the hemagglutinin H1 virus that caused the 1918 pandemic and another with the antibody glued to the hemagglutinin from the 2004 Vietnam H5 avian influenza.
The found that CR6261 latches on to the epitope of a virus, or the so-called stalk of the mushroom-like hemagglutinin particle. Most antibodies try to attack the mushroom cap of hemagglutinin proteins, because that is much more accessible.
Furthermore, when the scientists analyzed the genome of more than 5,000 different influenza viruses, they found that the epitope's sequence is nearly identical in all of them, suggesting that this part of the virus is much more highly conserved than the virus’ constantly mutating cap and thus a good target.
This insight into the way the CR6261 antibody binds to the virus' structure makes sense, the researchers say. It helps explains why the antibody may not be as powerful as it needs to be to attack influenza. “The epitope it needs to latch on to is at the base of the stalk of the hemagglutinin protein, so it is difficult to get to because these proteins are packed together tightly on the viral coat,” says first author, Damian Ekiert, a graduate student in the Scripps Research Kellogg School of Science and Technology.
“Plus, most antibodies try to attack the mushroom cap of the hemagglutinin proteins, because that is much more accessible, and so this probably sets up a huge competition between antibodies.”
The next step now is to figure out how to suppress reactivity with those regions and enhance the immune system's attack on this conserved epitope.
The team’s findings are published in the February 26 issue of Science Express.
2/26/2009
By the CEO's words Ronald Brus
Recently we expanded our set of influenza antibodies by discovering antibodies targeting also the H3 seasonal influenza strains.
Patents for these antibodies have been filed worldwide, based on the first filing date of September 7, 2006.
The claims encompass the unique conserved region to which the antibodies bind, the unique features of the neutralizing antibodies, their mode of binding, as well as their use in diagnosing, treating and preventing influenza virus infection and associated symptoms.
3/2/2009
This is quite educatived and informative in all ramification
12/1/2009
I would like to know how affective this new Molecule is against the Swine Flu Virus, which appears to be matastasizing. Anyone have an answer to this question? Over 50 children in my state have died as a direct result of the H1N1 virus. Thoughts, please.
ADVERTISEMENT
INTERVIEW:
NEW PROGNOSTIC GENETIC TEST FOR ADOLESCENT SCOLIOSIS - Interview with Dr. Baron Lonner, director of Scoliosis and Spine Associates
...MORE
NewsArticles BlogsADVERTISEMENT
Subscribe to RSS
Email
Print
Share
More GEN News Highlights
Listen
Save
Comment
View All