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.
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8 Comments
Add CommentSurely 500,000 people is not '10 to 20 percent of the world's population', at least in the world I'm living on.
Reply | Report Abuse | Link to thisYou're right, iooqxpooi, but that's not what the article says. It says influenza affects 10 to 20 percent of the population, and that of that group of infected people, 250,000 to 500,000 die of the flu each year.
Reply | Report Abuse | Link to thisIt sounds promising, and it may work. Influenza mutates rapidly, and any time there is evolutionary pressure, it will result in amplification of the viruses that survive.
Reply | Report Abuse | Link to thisBut - humans are more of an opportunistic host of influenza, not the primary one. So there should not be pressure at the core of the animal population that supports it.
90% seems a little on the low side for antibodies though. Just my thought.
this guy will surely do it.....n when he says that we are not prepared for an pandemic,,,that sounds serious..
Reply | Report Abuse | Link to thisIf the M2e-HBc particles caused the formation of antibodies against M2e, I don't understand how"The target is not the virus, but the target is the virus-infected cell." Does the M2e portion of the virus project through the cell surface before the virus is fully assembled inside the cell?
Reply | Report Abuse | Link to thisSusan A. Ryan
Ft. Collins, Co.
Humans more of an opportunistic host of influenza? I am not sure what strain you are referring to, but I am assuming the H5N1 avian flu. Yes the avian flu is an opportunistic infection of humans now, but the threat of the virulent H5N1 virus reassorting with the transmissable traits of the common flu can be disasterous. The virus is always going to be present in wild birds so to attack a virus that can be migrated around the world wound be daunting if not impossible. So the attack on the H5N1 virus must be consentrated on humans in order to prepare for a possible pandemic.
Reply | Report Abuse | Link to thisSusan,
Reply | Report Abuse | Link to thisThat is a very good question! I know that the virus' proteins and RNA are uncoated and released into the host cell, early after entry... but how soon after the cell is infected does it become an antigen presenting cell? Surely it needs to become an APC early on to be able to interrupt the virus from maturing in the host. Thanks for giving me something to ponder...
Historical Facts About Influenza:
Reply | Report Abuse | Link to thisThe last influenza pandemic occurred nearly 100 years ago, and resulted in about 50 million deaths worldwide. Those who survived have allowed others to obtain antibodies from them to develop other antibodies for future viral outbreaks that may occur. This last influenza pandemic also allowed others to obtain this virus from those who died as a result to facilitate effective treatments and vaccines for viral outbreaks that may happen in the future as well.
With influenza, it is understood that the disease influenza is a disease caused by a RNA virus that can infect both mammals and birds. In fact, this particular virus can mutate to where it can be shared between the two life forms and multiply within each one of them. Unlike coryza, influenza expresses symptoms more severely, and usually lasts two weeks until one recovers who has the flu. Influenza, however, poses a danger to some with compromised immune systems, such as the chronically ill. In cases such as this, influenza can in fact progress to deadly pneumonia. Symptoms of influenza usually start to express themselves symptomatically 36 hours after being infected with the virus. Over 10 percent of the population are infected with this virus every year- resulting in about 200,000 hospitalizations and nearly 40,000 deaths.
The flu vaccination contains three viral strains of suspected viruses for flu outbreaks during a particular winter season, as determined by the World Health Organization, as well as the Centers for Disease Control, and other organizations. Unfortunately, the influenza vaccine administered last flu season was largely ineffective due to unsuspected strains of the virus infecting others, although about 140 million doses of this vaccine were administered. After giving the vaccination dose to one, it takes about 10 days for that person to build up an immunity for the disease of influenza.
The influenza season peaks between the months of January and March. The vaccine for this influenza season is manufactured by 6 different companies. Yet the strains chosen are speculated influenza viruses, as this does not eliminate the chance of a new and dominant influenza viral strain that possibly could cause a pandemic. It takes manufacturers about 6 months to make and formulate the influenza vaccination. There is a vaccine for this illness that is produced every year according to which type of virus may be prevalent during a particular flu season. The vaccination is recommended to be administered to those who are at high risk, such as the chronically ill. Also, it is recommended that those under 18 years of age get the vaccine, as well as those people over the age of 50. Furthermore, those people who regularly take aspirin should receive the vaccine, as the influenza disease can become a catalyst for Reye’s Syndrome. Pregnant women should receive the vaccine as well- as there are many other vaccines available to fortunately prevent other diseases, perhaps.