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The flu is with us again, but maybe not forever

Two impressive articles in Science magazine caught my eye a few weeks ago. They suggest that it is possible to make a vaccine that will work against all flu viruses and will not have to be changed every year. How? Visualize influenza viruses as protein spheres containing eight segments of genetic material. Sticking out of this minute sphere are two spike-shaped proteins, Hemaglutinin and Neuraminidase, called H and N for short. (Proteins are made of amino acids stitched together in different sequences and can fold into a variety of shapes, including the spikes of influenza.) The virus, viewed in an electron microscope, reminds me of the anti-ship mines in old World War II movies: a ball of lethal explosives with protruding detonators. The H and N proteins give flu viruses their names — the 2009 pandemic virus was called H1N1 because it contained specific forms of H and N. According to a recent article by Rafael Medina and Adolfo Garcia-Sastre of the Mt. Sinai School of Medicine, there are 16 different forms of H and 9 forms of N among the various flu viruses infecting humans, birds, pigs and other animals. When two different viruses infect the same cell, in a bird lung say, they take it over to make more virus and in the process they can trade H, N and other genes and produce viruses with new, potentially lethal genetic combinations. Thus we can have H5N1, H7N7 or H3N2, depending on what’s brewing out there in birds and pigs. There is an H5N1 flu strain circulating in birds in Southeast Asia called highly pathogenic avian influenza virus. Since 1997, 562 human infections from this virus have been recorded in 15 countries and nearly 60 percent of those infected died, partly because the virus seems to infect deep in the human lung. The victims were mostly farmers in close contact with waterfowl or chickens. The H5N1 virus does not jump easily from one human to another as 2009’s less lethal H1N1 virus did. Viewers of the film “Contagion” (which is dramatic, but scientifically reasonable) will appreciate the consequences of a mutation of H5N1 that allows too-efficient human-to-human infection. It is always good to be warned about threats before they materialize. We once had a Distant Early Warning line, a series of radars in northern Canada, to detect Soviet missiles. In an analogous way, we have a DEW line run by the Centers for Disease Control and many cooperating national and international laboratories to detect incoming viruses. These people found H5N1 and are watching it so that we can plan for a breakout, but missed the 2009 H1N1 pandemic, which erupted with a new combination of pig, human and bird influenza virus genes. We may have some new tools. After a vaccination, our bodies create antibodies against the particular H molecules in the vaccine. These antibodies stick to the head of the H spike. This part of the molecule changes every year so that last year’s antibodies do not recognize this year’s virus — hence the need for yearly vaccination. But other parts of most H proteins do not vary year to year. Thus the amino acids that make up the shafts of H1 and the H5 are alike. Why our immune system tends to ignore this part of the molecule is not clear, but if we can trick it into making antibodies that stick to invariant parts of an H molecule, we might neutralize many types of virus.Now, two large international consortia of scientists have succeeded in making antibodies that bind to the shaft of all H molecules. These antibodies protect infected experimental mice from many forms of influenza virus and bring very sick mice back to health. What does this mean for human therapy? First, in serious flu cases, the antibodies, which are made in the laboratory from human DNA, could be used to inactivate the virus, slow the infection and perhaps save the patient. Second, a vaccine that contains bits of the H molecule’s shaft could stimulate the production of antibodies that protect against many flu viruses. One message of 2011 is that the natural world can throw disaster at us on a far larger scale than any terrorist. Yet it is much easier to appropriate money to fight human malefactors because they infuriate us in a way that natural disasters do not. In coming budget cuts, it would be wise to remember the power of nature and fund our public health measures. It will take a little time to decide whether better flu vaccines are in the offing. In the meantime, I got an old-fashioned flu shot. Richard Kessin, Ph.D., is professor of pathology and cell biology at Columbia University. He and his wife, Galene, live in Norfolk. He can be reached at rhk2@columbia.edu.

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