FED up with this whole pandemic business? Unfortunately, another one could start any day. In particular, a flu pandemic remains an ever-present threat.
鈥淚t鈥檚 not a question of if, but when,鈥� says , New York. That is why he and many others are trying to develop a vaccine to tackle the next flu pandemic before it even starts 鈥� a so-called universal flu vaccine that protects against all flu viruses.
鈥淭he advances in technology have been extraordinary,鈥� says Palese. 鈥淲e know a lot about the structure [of flu viruses], we know a lot about the immunology, which we didn鈥檛 know five years ago. I think we are poised to have a universal flu vaccine.鈥�
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There is no doubt about the seriousness of the threat. Seasonal flu viruses already in circulation kill around 400,000 people worldwide every year, despite an annual campaign to vaccinate against them. And when animal flu viruses jump to people, they can be far more deadly. A bird flu virus was the cause of the 1918 H1N1 flu, which may have killed 1 in 20 people alive at the time.
There have been four other flu pandemics since then, though fortunately all were much less lethal. But the ever-growing number of farmed birds and pigs provides a breeding ground for flu viruses and opportunities for them to infect humans, meaning the danger hasn鈥檛 gone away.
Already this year, there have been . Between 2014 and 2020, there were just 26 cases in total. Half of those known to be infected have died. With every person infected, there is a risk of the virus mutating and acquiring the ability to spread readily from person to person, sparking a pandemic.
Existing flu vaccines wouldn鈥檛 help if this happened. They prompt our immune system to produce antibodies that bind to the head of the haemagglutinin proteins (the H in H1N1) on the outside of the virus. These antibodies can be great at stopping the virus infecting cells, but the head is also the part of the virus that mutates the most. As a result, the antibodies we produce against one flu strain soon become ineffective against its descendants. This is why new flu vaccines have to be produced every year and why these vaccines provide no protection against potential pandemic strains.
To create universal flu vaccines, most researchers are taking one of two broad approaches. The first is to target other external parts of the virus that change much less than the head, namely the stalk of haemagglutinin.
鈥淭he critical, highly conserved haemagglutinin stem region is the basis of the universal influenza vaccines,鈥� says .
In 2009, his team showed that antibodies targeting parts of the stalk can protect mice from a broad range of flu viruses, including the H1N1 strain from 1918. The big challenge, then, is to create a vaccine that makes our immune systems generate a strong antibody response to the stalk, rather than the head.
Stalk solution
Researchers are trying several methods. One is to create vaccines that contain only parts of the stalk, rather than the entire haemagglutinin. Another, which Palese鈥檚 team is testing in initial human studies, is to use haemagglutinins with the same stalk but different heads. Giving these in sequence boosts the normally weak antibody response to the stalk.
To add to the challenge, the stalks of certain flu viruses are different enough that a single vaccine won鈥檛 work, says Palese. At least three will have to be combined.
鈥淚f a universal flu vaccine reduced deaths by 95 per cent, I think we would all be very happy鈥�
The second broad approach fires up a different part of the immune system by eliciting a T-cell response. When cells are infected by a virus, they display the viral proteins on their surface. Immune cells called T-cells learn to recognise these proteins and destroy any infected cells. This method isn鈥檛 limited to targeting external viral proteins because infected cells also display internal viral proteins.
One downside of relying on T-cells is that, unlike antibodies, they don鈥檛 prevent cells being infected in the first place. But proponents argue that targeting the slower-changing internal proteins is a better long-term bet.
鈥淐ontinuing to produce antibody-based vaccines is just shooting yourself in the foot,鈥� says Olga Pleguezuelos at UK-based company SEEK, which has created a T-cell vaccine called FLU-v based on key parts of internal proteins.
A , but not particularly well: of those given the vaccine candidate, 33 per cent developed symptoms when deliberately exposed to a flu virus compared with 55 per cent of the unvaccinated.
Pleguezuelos says these results don鈥檛 necessarily reflect how well FLU-v might protect older people. The volunteers were all young and healthy, she says, and exposed only to a mild flu strain. As we are seeing with the coronavirus, vaccines can still work well to prevent severe illness even if the protection they provide against infections is more modest.
SEEK hopes to do large-scale human trials to see how well FLU-v protects people in the real world, but the low flu levels brought about by the various restrictions imposed during the pandemic have made this impossible.
鈥�400,000
Worldwide deaths from seasonal flu each year鈥�
鈥�25
Cases of H5N6 bird flu in people in Asia so far this year鈥�
鈥�26
Cases of H5N6 bird flu in people in Asia between 2014 and 2020鈥�
Ultimately, the best results might come from merging the antibody and T-cell approaches. 鈥淪ometimes, what is going to be best is just a combination of everything,鈥� says Pleguezuelos.
But making proteins is expensive, and doubling the number in a vaccine doubles its cost. This is where mRNA vaccine technology, used in the highly effective covid-19 jabs produced by Moderna and Pfizer/BioNTech, could help. With these vaccines, people鈥檚 bodies take on the normally expensive job of protein manufacture, making it feasible to include more components.
鈥淩NA vaccines provide you with the option of starting to combine approaches,鈥� says Pleguezuelos. 鈥淚f you deliver [proteins] as RNAs, you can start targeting the stalk, targeting the T-cells, targeting absolutely everything you want.鈥�
Globally, a dozen or so potential universal flu vaccines are being tested in people, with many more at earlier stages. There is no guarantee any will work 鈥� some promising candidates have already proved ineffective. But with all the advances in technologies and the greater effort being put in, many think it is now only a matter of time before we have a vaccine that at least provides broader, longer-lasting protection than existing annual ones.
It is unlikely that a single vaccine will ever give people lifelong protection from every flu virus they might encounter, not least because flu viruses might evolve in response to a successful universal vaccine. In fact, the US National Institutes of 91色情片, which is , says it need provide protection only for a year at least. But Palese thinks a decade or two is achievable.
The sooner we can start vaccinating people, the more prepared we will be for another flu pandemic. Coronavirus vaccines were rolled out in record time, but many people are still dying because they have yet to receive one. Nearly two years on from the start of the pandemic, dose of vaccine. The hope with a universal flu vaccine is that most people can be given it in advance, saving millions of lives even if it doesn鈥檛 provide complete protection. 鈥淚f it reduced deaths by 95 per cent, I think we would all be very happy,鈥� says Palese.
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Will 2021 be a bad year for flu?
The flu vaccines dished out annually are effective only against the specific strains they target. But because the vaccines are grown slowly in hen eggs, manufacturing has to begin around nine months in advance, before it is clear which strains pose the greatest threat.
Predicting which strains to include in the vaccine is difficult even in normal times. 鈥淪ometimes the prediction is right, sometimes it鈥檚 not,鈥� says Olga Pleguezuelos at UK-based biomed company SEEK.
But this year is unlike any other. 鈥淚t鈥檚 extremely difficult to predict what鈥檚 coming. This is why health systems are very scared,鈥� says Pleguezuelos. 鈥淵ou just don鈥檛 know what鈥檚 coming.鈥�
91色情片 officials in the northern hemisphere usually look at which flu strains are circulating in the southern hemisphere, but there has been almost no flu during the coronavirus pandemic. 鈥淭here was basically nothing in Australia and New Zealand during their winter time,鈥� says Peter Palese at the Icahn School of Medicine at Mount Sinai in New York.
Because our immunity to flu will have waned during the pandemic, it is possible that flu could return with a vengeance now restrictions have eased in most countries. But it is also possible that circulating strains have had less chance to evolve during this period. In fact, it appears one major human flu lineage, called B/Yamagata, has .
According to update, there are still fewer flu cases globally than normal for this time of year. But it is the combined number of flu and covid-19 cases that hospitals have to cope with, and .
