Every year in February, the WHO reports which new strains are the best candidates for an epidemic. Sometimes they don't change, but sometimes they all change.
Do these seasonal vaccines have certain disadvantages?
Yes, the disadvantages are enormous. Currently, the preparation of classical vaccines is very expensive; you need huge numbers of fertilized chicken eggs, a whole infrastructure.
Secondly, we sometimes miss the strain that becomes active. Research has shown that when all the data are taken together, the prediction rate is about 80 to 90 percent. But there are examples where large vaccination programs have taken place where the wrong strain was targeted. And the great disadvantage is that if a pandemic arrives, we will not be prepared.
Why do researchers think that a pandemic could be likely?
All the information that we have seems to indicate that for the 1918 flu—the mother of all the pandemics, which killed 50 million people—could have been caused by a virus strain from birds. Now we know that influenza is common among all kinds of birds, but it could also come from another animal. There is the possibility that the bird flu will adapt itself for human-to-human transmission. This has not happened, but there have been some 250 people killed by the H5 strain in different areas of South Asia. There is a larger than 50 percent mortality if humans are infected. If you have 500 million of these viruses, you have a larger probability that among these viruses there is one or two mutants that have the required combination for spreading among humans. This is justifiably a great danger.
When transmission takes place between birds, they don't have an equivalent immune response like humans. Consequently, the virus doesn't change. With humans you will not have the same conservation of the virus. On the contrary, I'm strongly convinced that if in Hong Kong, or somewhere else, a pandemic started to develop, it will quickly spread throughout the world, but there will be no immune defenses because nobody had been previously exposed.
So your solution is a universal vaccine.
You need a vaccine that is not invalidated by drift and shift. We've researched this via many years and PhDs. At the end of the 1980s and during the early 1990s we started thinking that a new approach that proved successful might lead to a universal vaccine.
If you have a pathogen—a virus—that infects man, most people will survive. The recovered person now has convalescence serum—that is, a serum that contains antibodies against the pathogen. With the antibodies we look for which viral proteins are their targets. If we identify these, we can create a vaccine, which targets these proteins. But in the case of drift, you need another strategy.
We found that besides the large HA (hemagglutinin) and NA (neuraminidase) there is a small protein, M2e, which does occur on the virus in very small quantities. So people didn't view it as important, but for us it was very important because it does not elicit anti-M2e in the majority of recovering people.
In other words, the virus's M2e does not naturally set off an immune response in humans. How do you get the immune system to target that small protein, then?
We have made it highly immunogenic by implanting it on a viruslike particle, so that if we present this in this way to the immune system, it is very immunogenic. M2e is only slightly present on the virus, but in the lung epithelium cells where the virus ends up and starts multiplying, in the invaded cells, M2e becomes abundant. The target is not the virus, but the virus-infected cell. If you, at an early stage, can kill off these cells, than you will counteract the infection.
Why doesn't the virus's M2e gene vary the way the HA and NA genes do?
In part, because of the absence of immune selection, which plays a role in the introduction of drift, so there are not many antibodies. But there is also the fact that M1 and M2 [to which M2e is attached] are coded by two overlapping genes. M1 has very important functions at several levels, which strongly restricts the variability of both M1 and M2. Any mutations in them will impede the virus from reproducing.