Dr. Ian Wilson
As the recent threat of swine flu has reminded us: influenza poses a significant and very real threat to human health. According to the U.S. Centers for Disease Control, more than 200,000 Americans are typically hospitalized from flu complications every year, and about 36,000 people die from the illness. But that is in a normal year. Over the past century, three major human influenza pandemics (the Spanish Flu of 1918-1919, the Asian Flu of 1957-1958, and the Hong Kong Flu of 1968-1969) have devastated the human population, killing around 50-100 million people worldwide.
Current flu vaccines offer protection only for the specific strains of influenza that public health officials believe to be currently circulating in the population. This involves a lot of guesswork about which strains will be most prevalent and, because the virus is constantly mutating, this guesswork must be repeated year after year.
Hoping to end this exercise of wheel-spinning, a group of scientists at Scripps Research and collaborating institutions around the world have been searching for a molecular target common to many or all strains of influenza, which would enable the development of a universal vaccine. This search just made a great leap forward.
Ian Wilson was recently featured on NPR's "Talk of the Nation," discussing how the work being done at Scripps Research could create a vaccine that fights all flu strains and triggers the body to fight more kinds of viruses.
In a paper published in Science Express, Professor Ian Wilson's team reports the characterization of an immune system molecule that targets what appears to be an "Achilles heel" of a wide range of influenza viruses – including the viruses responsible for past global pandemics, those causing current common infections, and strains of bird flu believed to pose future world threats.
The study, a collaboration between Scripps Research scientists and researchers at the Dutch biopharmaceutical company Crucell, centered on an antibody known as CR6261, which was found to attach to the virus that caused the devastating 1918 "Spanish flu" and to a virus of the "H5" class of avian influenza that jumped from chickens to a human in Vietnam in 2004.
"We can see exactly how and where the antibody grabs on to these influenza viruses," says the study's first author, Damian Ekiert, a graduate student in the Scripps Research Kellogg School of Science and Technology working in the Wilson laboratory. "And we can see that this same mode of interaction occurs in viruses that are very different from each other."
The key to CR6261's effectiveness appears to be in where it attacks the virus. Influenza antibodies, including those induced by current vaccines, target mushroom-shaped proteins known as hemagglutinin (HA) that stud the outer coat of a virus particle to help the virus infect cells of a host organism, such as humans.
What the Scripps Research scientists found, however, is that CR6261 latches on to the "stalk" of the mushroom-like hemagglutinin particle, near where the protein juts out from the viral coat, and that this binding area, known as an epitope, is the same in both the H1 and H5 viruses. After analyzing the genome of more than 5,000 different influenza viruses, the scientists found 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's constantly mutating cap.
"Certain regions of the hemagglutinin protein are like big red flags to the immune system, but they are functionally unimportant," Wilson says. "The task now is to figure out how to suppress reactivity with those regions and enhance the immune system's attack on this conserved epitope."
As the team sets out to answer the next set of questions, their work is buttressed by the potential and the excitement of their findings. "I have been working with influenza virus antigens since 1987, and I find it just amazing to suddenly see antibodies now appear that we had no idea existed," Wilson says.
Wislon attributes the discovery, in large part, to the modern technology at the team's disposal at Scripps Research. Phage display was used to isolate antibodies from human blood, and the state-of-the-art robotic crystallization laboratory enabled the team to understand the structures of microbial antigens much more quickly than previously possible.
The value of the team's findings is priceless, but the technology that fuels their work is not. Your support can help ensure that Scripps Research's top scientific minds continue to have the best tools available to bring tomorrow's biomedical advances today.