Researchers Discover Antibody That Fights Multiple Flu Strains

In a major new discovery that could help prevent or treat influenza, researchers have identified an antibody that blocks the flu virus from entering its hosts’ cells and that can be used to cure already infected animals. The findings were reported in the most recent edition of the journal Nature.

Before a virus can make us sick, it must first adsorb (bind) to the surface of our cells and then get its DNA or RNA into our cells. Influenza A viruses use a protein on their surface called Hemagglutinin to attach to their hosts’ cells. Hemagglutinin is abbreviated “H” and the particular variety of Hemagglutinin forms part of the strain’s name (e.g., H1N1 or H5N1).  The “N” comes from an enzyme the virus produces called neuraminidase, which it uses to lyse (burst) its hosts’ cells in order to release newly formed virus particles.

The antibody discovered by lead author Ian Wilson (Scripps Research Institute) and colleagues at Scripps and Sea Lane Biotechnologies, binds to hemagglutinin thus preventing infection. This discovery may help in the development of more effective vaccines against the flu virus, which kills an average of 35,000 people per year in the U.S. alone. It could also help avert a deadly pandemic of avian influenza.

The research began by creating a library of antibodies from thousands of flu survivors from around the world by mining their bone marrow, which acts like a repository for all the antibodies they have ever made, the Bay Citizen reports. From this library, they were able to narrow their search to just the ones able to bind to influenza A. From this subset, they came upon the C05 antibody which protected cells growing in a Petri dish from influenza A infection. They also tried the experiment in vivo and found that C05 prevented mice from being infected. Furthermore, they discovered that mice already infected with a deadly strain of influenza were 100% cured when exposed to C05.

Perhaps the most exciting aspect of this research is that C05 binds to hemagglutinin, which is highly conserved genetically and used by many different strains to infect their hosts. Consequently, C05 is effective against several different varieties of influenza, including H1, H2, H3 and H9 strains. If C05 proves effective in preventing or treating human infections, this could be a major breakthrough, as we currently have little or no natural immunity to H9 strains and there is at least one highly pathogenic avian influenza H9 strain that has already wreaked havoc on some poultry flocks. This deadly strain could acquire person to person transmissibility through gene exchange with other flu viruses, as several H1 and H3 strains have already done, thus becoming the next deadly pandemic strain.

Bird Flu Paper Going To Press

In December I wrote about how two different research groups had stitched together new varieties of the deadly H5N1 Bird Flu that were easily transmissible between ferrets through droplets in the air. Many were worried that if their results were published, terrorists could use the data to create a devastating biological weapon. As a result, publication of both papers was put on hold. However, the paper by Yoshihiro Kawaoka and colleagues at the University of Wisconsin, Madison and Tokyo, is now set to be published in Nature (see “One H5N1 Paper Finally Goes to Press,” in Science, May 4, 2012). The second paper, by Ron Fouchier and colleagues at Erasmus MC, Rotterdam, Netherlands, has been delayed by bureaucratic red tape, but is slated to be published by Science.

Wild avian influenza strains are currently not easily transmissible from person to person and are overwhelmingly contracted only through direct contact with infected birds. Yet for those who do contract the virus, the mortality rate has been terrifyingly high (around 60%). Virologists have been predicting for years that this or another highly pathogenic avian influenza (HPAI) strain could mutate and develop person-to-person transmissibility (like seasonal flus), leading to a deadly pandemic like the one in 1918, which killed between 50 and 100 million people worldwide.

Scientists argue that research like that conducted by the Fouchier and Kawaoka teams is essential for understanding how influenza viruses mutate and develop phenotypes that are dangerous to humans. This information would be helpful in terms of assessing pandemic risks and in terms of veterinary monitoring. For example, birds that are discovered carrying viruses with the necessary mutations could be immediately culled and monitoring increased in areas where they are discovered.

Kawaoka et al discovered that four mutations on the Hemaglutanin (the “H” in H5N1) protein would allow respiratory transmission of the virus in ferrets, which are one of the closest animals models to humans. Most influenza strains that are easily transmissible between ferrets are also easily transmissible between people. The same is not always true for bird strains.

While these new strains can spread easily through the air between ferrets, they were far less deadly than wild H5N1 and even though ferrets tend to be a good approximation for the effect in humans, scientists do not know if these new strains will in fact spread between people. Furthermore, it is not trivial to make virulent strains of influenza. The equipment, facilities and expertise necessary to produce virulent new strains of influenza are not easy to come by and it is unlikely that any terrorists would have the skill and access to the necessary materials.