Predicting which fast-mutating influenza viruses will dominate the flu season more than six months before it happens is notoriously difficult yet the ponderous global vaccine production process demands maximum lead time. So, scientists have to take their best guess based on the available data.
In March, the WHO rolled out its recommended composition for flu vaccines in the Northern Hemisphere. (It announced its next Southern Hemisphere recommendations six months or so later.) For northern climes, the WHO proposes a cocktail of H1N1, H3N2 and a B virus—and for those interested in a quadrivalent vaccine, a dash of B/Phuket/3073/2013-like virus.
For an explanation on the process for making vaccines and related issues, Global Health Now spoke this spring to Andrew Pekosz, director of the Center for Emerging Viruses and Infectious Diseases at the Johns Hopkins Bloomberg School of Public Health.
Are there any surprises in WHO’s recommendations?
No surprises. The recommendation for this year’s Northern Hemisphere vaccine turns out to be exactly the same as those made six months ago for the Southern Hemisphere. The biggest thing was an update of the H1N1 component of the vaccine, which had not been changed in eight years. That was updated to a recent strain. There had been some controversy over whether or not that [component in the] vaccine was doing a good job in terms of providing protection against circulating H1N1 strains. So, WHO decided to update it.
Is that how the vaccine development generally flows from South to North?
The seasons [in the two hemispheres] are diametrically opposed. We pay close attention to what happens in the Southern Hemisphere during their winter (our summer) because that then gives us an even better idea of virus strains that will be circulating here when winter comes around. But it doesn’t help us with our vaccine strain choices because that has to be done earlier in the year. That has to be decided at least six months before we want to start vaccinating people.
For the Northern Hemisphere, the vaccine strain is picked in March based on what’s circulating in January and February. While vaccine manufacturers make vaccines, we see how flu goes in the Southern Hemisphere to see if our predictions hold true there.
Any way to close that gap between predictions of the strains to include in a vaccine and the delivery of the vaccine?
Vaccine production occupies the biggest chunk of that time. If we are going to buy time to choose vaccine strains, we really have to find a better and faster way to make a flu vaccine. We make the choice of vaccine in March when we are still in the middle of flu season in the US. We’ve chosen it before we know how the end of flu season turns out.
Are we better at predicting flu viruses to include in vaccines now than we were a couple decades ago?
Yes. We’re better at doing things like sequencing viruses. We collect many more influenza virus strains and characterize them during flu season and much of this is done in a close to real time manner. At any one time, we have a very good idea of what viruses are circulating in the human population.
So, if we know better what’s out there circulating, wouldn’t that translate to better vaccines and fewer cases of influenza?
We have more information but that doesn’t make the prediction process easier because at the end of day we’re often left with the choice between several virus strains that might be good for the vaccine. Oftentimes we aren’t sure which of those will become the dominant virus. We’re still lagging behind—saying this is circulating now but we can’t say this one virus will be the one dominant virus next flu season.
What does your intuition tell you about the accuracy of this year’s recommendations? Do you have gut feeling on these?
That’s always there because it is unlinked from the vaccine choice pathway. I can have a higher success rate because I have more time to analyze the virus strains that are circulating. At our influenza center at Hopkins, in the next two weeks, we will be analyzing 75 influenza viruses collected here and have a better idea of what’s circulating in March. If that’s the same as what was circulating in February and January, we will be okay. If something has changed, that informs us how effective the vaccine will be, but it won’t affect the vaccine choice or the production pipeline.
How’s this year’s flu vaccine in the US working out?
The flu vaccine this year is only in the 40 to 50 percent effective range. It’s on the bad end of what we expect. We predicted it would be much better at inducing protection than it has been. On paper the vaccine strain and the circulating strain seem to be well matched but the vaccine efficacy data doesn’t reflect that. We’ve got to figure out what we’re missing this year.
Why isn’t the H7N9 avian flu virus that seems to be surging in China in this recommendation? Its 5th epidemic has infected more than 460 people since last fall.
That epidemic is really focused completely in people coming in contact with infected poultry. There are minimal reports of human to human transmission with that virus.
What we don’t know yet is why there is such a significant increase this year in H7N9 cases. It may just be chance. It may be the virus changed and became more effective at infecting poultry. Or worst case scenario, it is more effective at infecting humans. We’re in the middle of trying to figure that out right now.
Given the potential effects of an H7N9 pandemic, wouldn’t it be prudent to include that virus in a vaccine?
That would be difficult at this time because it would take away production facilities currently dedicated for production of the vaccine for seasonal influenza, which we know will happen next winter as it always does.
There has been significant work done on an H7 vaccine in the past few years. Many scientific agencies, including the US NIH, WHO, and European science agencies have recognized the potential risk of H7, and international research projects have generated candidate vaccines for that virus. It turns out to be a tricky virus because it doesn’t work as well as most other strains of influenza when you turn it into a vaccine. There has been significant work done to make it a more effective vaccine through adjuvants or multiple inoculations.
That’s where basic science research helps us in preparation for a pandemic. If we thought we could make an H7 flu vaccine as easily as we can with seasonal flu, we would have been wrong. We can make effective H7 vaccines but they need to be modified. We wouldn’t have known that unless we began basic research studies on it several years ago in preparation for its potential risk.
What number of cases of H7N9 or event would make you worried?
It all comes down to sustained human to human transmission. Getting the virus from poultry is one thing. Having a close relation or maybe a health care worker acquire it from a patient is another thing, but sustained transmission outside of a hospital setting would be the real bellwether that something has changed about this virus and it is starting to become a very significant risk.
And the one thing you can count on with viruses is they will change.
Right, exactly. That even applies to seasonal flu. Some of our efforts really show a lot of change happens in seasonal flu that may be impacting the disease potential of the virus. It’s going on all the time.
When we think of flu epidemics, our reference point is the 1918 flu. How likely is a repeat of a pandemic of that scale?
There are a lot of societal and economic factors that contributed to the 1918 pandemic which we certainly don’t have today.
A world at war.
Right. The soldiers in army camps as means of helping spread the virus initially. The general lack of antibiotics to deal with secondary bacterial infections, which are a common cause of very severe disease. And the health of populations has improved tremendously. I think it’s unlikely we will ever see another pandemic [like that], but we certainly expect to see more flu pandemics that are severe. In 2009, we were fortunate that the virus wasn’t very virulent. It didn’t cause excessive amounts of disease. There are a lot of viruses like the H7 that can be expected to cause a high number of serious illnesses.
But you’re still able to sleep at night?
Yes, I still am.