WALTER FIERS AIMING FOR M2e: Found a protein segment, called M2e, on the influenza virus that may lead to a universal vaccine, thereby eliminating annual shots and protecting against pandemics.
VIRAL TOLL: The influenza virus infects about 10 to 20 percent of the world's population annually, killing 250,000 to 500,000. Past pandemics ensnared about 30 to 50 percent of the population; the 1918 pandemic caused about 50 million deaths.
DELIVERY OPTIONS: In terms of administering a vaccine during a pandemic, Fiers argues for the development of a nasal spray: "Medical workers injecting people will be too slow." Image: NICOLAS GUERIN
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Ingmar Bergman’s famous 1957 movie The Seventh Seal takes place during the 14th century, when Europe is in the midst of a major epidemic of the bubonic plague—the Black Death—which ultimately killed about half the population. A Swedish knight, Antonius Block, returns from the Crusades and finds Death waiting for him. He challenges Death, later seen disguised as a priest, to a chess match, hoping to stave off his own death by devising what he hopes is a winning next move.
For the past three decades, researchers and health workers have engaged in a similar battle against one of the most cunning viruses to afflict humanity and much of the animal world: the dread influenza virus. This pathogen is even smarter than Death; it continuously changes the appearance of its chess pawns—the proteins on its coat—so that im-mune systems do not recognize the new disguise.
Every year the World Health Organization and other institutions try to predict the next change in the virus’s coat. Once the WHO decides on the likeliest alterations, drug manufacturers then have only a few months to develop vaccines. “The whole infrastructure required for the preparation of seasonal vaccines has enormous disadvantages,” remarks Walter Fiers, a molecular biologist at Ghent University in Belgium. “It is slow—sometimes we miss the strain that becomes predominant—and if a pandemic should arrive, we will not be prepared.” Fiers’s goal: a universal vaccine that, like some childhood immunizations, would confer lifelong immunity.
Scientists have dreamed for decades of a one-shot approach to stop the flu—particularly influenza A, the most serious type. But the task is daunting. The appearance-changing coat of the influenza virus is studded with mainly two proteins: hemagglutinin, which allows the virus to attach to and enter a cell; and neuraminidase, which boosts the virus’s ability to pass to other cells. (These proteins serve as the basis for influenza nomenclature; for instance, the H5N1 virus refers to specific classes of hemagglutinin and neuraminidase, which in this example correspond to an avian flu subtype.) The genes responsible for these proteins undergo frequent point mutations, resulting in genetic “drift”; moreover, the genes from different animal and human strains may also interchange, resulting in genetic “shift.” Both drift and shift make these proteins unrecognizable to the antibodies present in people that were previously inoculated against the flu virus, which now circulates as more than 90 strains.
Unlike the hapless knight Block, the 77-year-old Fiers believes that he has found his adversary’s Achilles’ heel: although the virus is good at disguising its pawns, there is one on its coat that it cannot change. That pawn, the external part of a protein called M2, should be the target for vaccination, he says.
Fiers has come to this conclusion after five decades of work in molecular biology—in particular, decoding genomes. In 1972 he and his team were the first to publish the nucleotide sequence of a complete gene. This gene codes for the coat protein of a bacteria-infecting virus, or bacteriophage. Four years later they published the bacteriophage’s complete genome—all four genes of it. “This was the first complete genome that was sequenced,” Fiers recalls. Because of its medical importance, he decided around that time to focus on the influenza virus.