June 11, 2014

expert reaction to pandemic potential of circulating influenza viruses

A study published in Cell Host & Microbe reported that circulating bird flu viruses are very similar to the flu virus that caused the 1918 pandemic—the most devastating disease outbreak ever recorded.

Prof Wendy Barclay, Chair in Influenza Virology, Imperial College London, said:

“Influenza viruses that exist in nature in wild birds shuffle their genes about all the time and create novel viruses with new genetic combinations. In this way a virus was created by nature that in 1918 replicated well and transmitted efficiently in humans.  In their new paper, Kawaoka’s group have recreated those historical events by mixing together a set of genes taken from viruses of wild birds, and adding in some adaptive changes like those selected during virus replication in mammals such as humans or pigs. They created a virus that was transmissible and virulent in ferrets, the best model for human flu. By retracing the evolutionary steps that created the 1918 virus, they re-enact how the virus can switch from harmless avian virus to a potentially pandemic one. But just because the scientists could make this virus does not mean to say that nature will inevitably do so. What we still lack from this work is a quantitation of the risk; how many rolls of the dice would it take for this scenario to arise today?

“What the work does show is that the 1918 virus was not a ‘one off’ and that knowledge can be used to justify further research to help combat future influenza outbreaks including stockpiling of drugs and renewing of pandemic plans. Reassuringly the virus that was created was recognized by antibodies from people vaccinated against the modern day 2009 pandemic influenza. This suggests that if it were to escape the lab it would not be good at infecting and spreading in people today as most of us already have that type of antibody as a result of being vaccinated or naturally infected since 2009. This type of knowledge does form part of the risk assessment that scientists perform before they begin this type of work and which is updated as the experiment proceeds.

“The data also have implications for vaccine production because the new virus that transmitted in ferrets differed from the starting avian virus in its recognition by antibodies. This suggests that ‘prepandemic’ vaccines generated using original avian viruses before a pandemic virus emerges may not work as well as we would hope. With this new knowledge we might be able to pre-empt the changes and correct that deficit.

“It is important with this type of work to make sure we do learn as much new information as possible from each experiment and always to ask ourselves as scientists if we could learn these things in a safer way. Sometimes that is possible but it is difficult to envisage how that could be in this particular case.”

Dr Ben Neuman, Virologist, University of Reading, said:

“One of the reasons that scientists do experiments is to predict the future – in this case, to catch and prevent epidemics before they happen.  These researchers have identified some potentially very dangerous flu viruses that are circulating in birds, and have shown that they could potentially spread between people with a few small changes.  However, it is worth remembering that past pandemics including the 2008 “swine” flu came from unexpected sources.

“The viruses described in this paper resemble one that killed millions at the end of World War I, which sounds quite worrying at first.  However, it is important to remember that these viruses are not new – just newly discovered.  Much of what makes a virus go pandemic is not related to disease, but to mundane changes that make the virus a little bit more efficient at growing in people.  These are probably direct descendants of the virus that led to the 1918 Spanish flu, but if so, that means that we have been sharing the planet with them for nearly a century without major incident.

“Another important consideration is how well the new virus is able to compete with the viruses that are already out there.  It is also worth looking at what happened to the descendants of the 1918 flu, which gradually morphed into the ordinary seasonal flu before being driven to extinction in the human population by the arrival of “swine” flu in 2008.  So, even if an exact copy of the 1918 flu were to reappear, it is not certain that it would spread as well or be as severe the second time around.

“This paper shows once again that the world is full of viruses, some with more potential to harm than others.  But for most, that potential will never be realised.  These viruses are fascinating, and it is certainly worth studying them and watching how they spread, but right now there is no good reason to worry.”

Additional comments from Dr Ben Neuman:

“The flu virus is more careful than most, but in a typical day in a typical infected person we can expect that the virus will have made every single random change that it is possible to make, probably every combination of two random changes, along with some more exotic changes.  Despite this, the virus changes fairly slowly because it is a complicated biological machine, and most random changes break the machinery.  Use the analogy of a car: if you were to randomly exchange a spark plug for other household items, would your changes be likely to improve the car?

“So somewhere in the world, viruses with the mutations made in this paper have already been made, and will likely be made again.  This paper describes potentially dangerous experiments, which would need to have been performed with the most careful precautions.  But these changes happen in the wild, and when they happen in a lab, at least we can study them.  And studying things that can have a big impact on human health is a big part of why scientists are here.”

Prof Peter Openshaw, Director of the Centre for Respiratory Infection, Imperial College London, said:

“These very well-performed studies underscore the need for close monitoring of the viruses that are currently circulating in birds.

“There is certainly no reason to be complacent – the swine flu outbreak may have been mild by comparison to the sorts of outbreaks that these viruses could cause, but it still stretched our resources to the limit.

“This paper shows that there are strains of flu around that are only a few short steps from being highly transmissible between people. The worst case scenario is that a virus could emerge that has antiviral and vaccine resistance, droplet transmissibility and high-severity traits all rolled into one. It would not take many mutations for the viruses now around in birds to make that leap.

“Let’s hope that does not happen, but continue to update our strategic plans.”

‘Circulating avian influenza viruses closely related to the 1918 virus have pandemic potential’ by Tokiko Watanabe et al. published in Cell Host & Microbe on Wednesday 11 June 2014.

Declared interests

Peter Openshaw’s research is funded by the Wellcome Trust, the MRC, BBSRC and the European Union. He has received honoraria or consultancy fees from GSK, Janssen, Johnston and Johnston and Sanofi.