In 1980 Fiers first sequenced the gene for hemagglutinin derived from the human influenza strain H3N2 that circulated in 1965. He then compared the hemagglutinin gene of this strain with a similar hemagglutinin gene derived from the strain that had started the 1968 Hong Kong pandemic. His analysis proved that point mutations account for genetic drift.
Equally important, his studies led him to see how the virus can jump species through genetic shifts. At that time scientists knew that antibodies from people infected by the 1968 pandemic virus also reacted with an influenza strain isolated in 1963 from flu-ridden ducks. Fiers investigated the nucleotide sequence of the hemagglutinin gene of this duck virus and found that it was indeed very closely related to the strain that started the 1968 Hong Kong outbreak. Today infectious disease experts recognize that an avian flu virus could genetically change enough to trigger a human pandemic.
If such a jump occurred, the virus “would not be hindered by any preexisting immunity in the human population,” Fiers explains. “It would spread fast over the world because when it arrived here it would look like an entirely different virus. Therefore, you need a vaccine that is not invalidated by drift or shift.”
More specifically, he needed a vaccine based on a part of the influenza virus that does not change. Fiers found it in the viral coat protein M2, which creates a pore in the coat. Specifically, he noticed that a section of that protein, called M2e, remains stable even as the other viral surface proteins mutate. The M2 protein, however, occurs only in small numbers on the virus, which is too low to set off a good immune response.
The obvious solution was to amplify the number of M2e segments. But how? Fiers turned to the liver-attacking hepatitis B virus. This pathogen has an inner protein core called HBc, and something intriguing happens when the gene for HBc is inserted into the bacterium Escherichia coli. The bacterium starts producing HBc proteins and assembles them to produce viruslike particles. Fiers found that by linking M2e genes to HBc genes, the bacteria would produce viruslike particles studded with M2e.
In tests with mice and, later, ferrets, the M2e-HBc particles caused the formation of antibodies directed against M2e, thereby protecting the animals from a lethal dose of influenza. The vaccine works differently from conventional vaccines in that it does not prevent infection directly. “The target is not the virus, but the target is the virus-infected cell,” Fiers says. “If at an early stage, you can kill off these cells, then you will counteract the infection.”
In 1997 Fiers received a patent for the technology, and in 1999 he published a paper in Nature Medicine expounding his approach. The British-American company Acambis, based in Cambridge, Mass., and Cambridge, England, has obtained the license to start production of the vaccine. In a phase I trial completed last year, Acambis found that among the 79 volunteers who received the vaccine, 90 percent developed antibodies to the M2e segment.
Whether the antibodies protect against influenza now needs to be determined—no guarantee if the past is any guide. A decade ago a drug based on an internal protein of the flu virus, called NP (for nucleoprotein), set the immune system’s killer T cells into action, but it only partially protected mice from the flu.
Because intentionally infecting a volunteer to see if a vaccine works is unethical, the compound will have to face large field trials. “We have to find an area where there is a higher probability that an influenza epidemic will take place,” Fiers says. The likeliest places are where dense human populations live near farm animals. Thousands of people will have to be vaccinated to obtain statistically acceptable results. (The current version of the M2 vaccine would protect only against influenza A, the type that has launched pandemics.)
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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.