Health

Will this year's jab protect us from a deadly flu epidemic?

The flu virus usually kills thousands, and experts are worried this season could be a bad one. With the annual flu vaccination programme getting underway this month, Lucy Elkins goes on the front line in the lab designed to spot the next fatal strain before it's too late

Experts say it is important to be vaccinated this winter because of fears we could be hit by a high number of flu cases - Covid restrictions meant there were fewer flu infections than normal last winter, thus the population at large has less immunity
Experts say it is important to be vaccinated this winter because of fears we could be hit by a high number of flu cases - Covid restrictions meant there were fewer flu infections than normal last winter, thus the population at large has less immunity Experts say it is important to be vaccinated this winter because of fears we could be hit by a high number of flu cases - Covid restrictions meant there were fewer flu infections than normal last winter, thus the population at large has less immunity

IT is only midday, but virologist Lynne Whittaker has already been hard at work for five hours without a break, fully masked and gloved up while she runs tests in a laboratory that, for safety's sake, is biosecure and firmly closed to visitors.

The reason for the caution is that she is analysing virus samples fresh off the plane from China. These are not, as you might expect, coronavirus samples, but nasal swabs from 15 people who have recently become ill with flu.

The tests that this senior research laboratory scientist is running will determine if this is a familiar virus or - more troubling - a new form that's capable of causing a pandemic.

No visitor is allowed into the lab until the tests have been completed and the samples secured back into storage fridges, as these contain live viruses and could potentially cause infection.

This all sounds a bit alarming and even James Bond-esque: as I watch through glass windows, I feel as if I'm on the film set for a pandemic disaster movie. And all this for ordinary old flu.

Except that while to the scientists based here, at the Worldwide Influenza Centre at the Francis Crick Institute in London, it's all in a day's work, this is deadly serious stuff. These tests will help determine what goes into your flu jab.

As this winter's vaccine rollout is set to be the biggest yet, this work is arguably more important than ever before.

That's because there are fears we could be hit by a high number of flu cases - Covid restrictions meant there were fewer flu infections than normal last winter, thus the population at large has less immunity.

In a typical year, around 10,000 in the UK die from flu, says Prof Andrew Easton, a virologist at the University of Warwick: "People who have flu are then susceptible to other infections - such as pneumonia - and the number of deaths can rise much higher."

The surveillance centre at the Francis Crick Institute plays a key role in determining how effective the vaccine will be.

Established in the 1950s (in another London location), it's one of seven around the world (the others are in Atlanta and Memphis in the US, Melbourne in Australia, Beijing in China, Tokyo in Japan and Siberia).

These surveillance centres are constantly analysing samples sent to them from around the world, to monitor the types of flu in circulation, how the common viruses are changing - and to keep their eyes open for the emergence of new, more troubling varieties such as the swine flu that appeared in 2009.

Each year the team at the Francis Crick Institute is sent 7,000 to 8,000 samples, collected using PCR tests conducted at some of the 150 associated national influenza centres dotted around the world.

"Which country sends its samples where, is, to some degree, historical - we get samples from Europe, West and South Africa, central Asia and Hong Kong," says Dr John McCauley, a virologist and director of the Worldwide Influenza Centre in London.

He says there are millions of flu viruses in circulation each year, but as Lynne Whittaker explains: "If we see something new emerging from just one country, we don't worry too much. However, if you are spotting that a new mutation is all around the place, that's when you worry."

Based on their analysis, the centres must predict which strains of the flu virus may dominate in the months ahead.

Twice a year, 30 representatives from the seven global surveillance centres get together to share their information - and views - about which types of flu are most likely to pose a threat.

The meetings are held in February to decide what goes into the northern hemisphere jabs (administered from now) and in September to decide what goes into the southern hemisphere jabs (administered six months later).

It's done this far in advance because it takes manufacturers up to six months to make the vaccine, says Dr McCauley.

These meetings aren't a formality: the committee must agree on which flu viruses go into vaccines and there can be disagreement.

"You have different views with regards to the recommendations," says Dr McCauley, choosing his words carefully.

"But then if you don't get a consensus we have a vote and the majority vote would then decide what's done - you don't always need it, but sometimes you do," he concedes.

Between 2015 and 2020, the flu jab prevented 15 to 52 per cent of flu infections - some years it was less effective than others.

And with little flu in the community last year - there were no flu hospital admissions at all in some parts of the UK last winter - some have questioned how accurate the prediction will be this year.

If the scientists predict it right, it could save thousands of lives. If not, cases - and deaths - can rocket, as happened in the winter of 2014/15.

Earlier in that year, scientists from around the world had predicted that strains of flu that had been circulating in Texas and Massachusetts would be dominant.

In fact, a Swiss strain became more dominant, and as a result, the vaccine was only 34 per cent effective in this country.

By January 2015, the viruses in the jab were so out-of-kilter with what was circulating that the effectiveness briefly dropped to 3 per cent, according to official data. Almost 30,000 people in England and Wales alone died of flu and pneumonia in 2015, compared with 25,000 the year before.

In 2018, the vaccine was just 15 per cent effective - and this prompted a change in the make-up of UK vaccines, with the addition of an adjuvant, an ingredient that boosts the immune response, in the jab for the over-65s.

Virologists are constantly working to develop flu vaccines so they offer protection from what scientists believe will be the season's dominant virus
Virologists are constantly working to develop flu vaccines so they offer protection from what scientists believe will be the season's dominant virus Virologists are constantly working to develop flu vaccines so they offer protection from what scientists believe will be the season's dominant virus

Adding an adjuvant may cause more swelling at the vaccination site, as it creates a stronger response. However, suggestions that adjuvants such as aluminium salts may cause other health problems have been discredited.

Meanwhile, the main vaccine given to 18 to 65-year-olds was changed to protect against four types of flu, not three as before.

This seemed to pay off: the 2019/20 vaccines fared better, with as much as 64 per cent effectiveness for those aged 18 to 64, figures from Public Health England show.

But the problem remains that once that decision is made about what's going into this year's vaccines, it's impossible to hit the brakes.

Cultivating the viruses needed for the vaccine and sourcing the components takes time, which means they can't start again, even when the types not earmarked for the vaccine suddenly start to circulate more widely.

"This came up in 2014 when some new viruses were identified probably at the end of March or beginning of April," says Dr McCauley.

"But even then - a month after the northern hemisphere meeting had taken place - the process had gone too far to be able to stop.

"The only alternative is that the government could have produced a single element vaccine to prevent that new strain, but that didn't happen," says Dr McCauley.

Making the prediction about which flu strain will dominate is, in many ways, an unenviable task.

As Prof Easton points out: "The difficulty is that the surveillance system is very elegant but trying to predict the strain that will cause problems in six months' time is a very big ask."

And predicting what lies ahead this year has been complicated by lockdown restrictions. During the last flu season (from October until April in this country) there was only one hospital admission for flu in Wales and Northern Ireland and one in Scotland; in England there were 131, compared to 1,691 the previous year.

In August, Dr Beverly Taylor from Seqirus, a major manufacturer of the flu jab, said there was a "big reduction" globally in labs supplying flu surveillance data and predicted "we could see a mismatch for at least one of the subtypes" in the vaccine for this winter as a result.

But Dr McCauley prickles at the suggestion that the surveillance may be less complete than normal.

"The amount of flu in circulation went down - but the amount of surveillance didn't," he says.

"Yes, OK, we are looking at a smaller pool [of flu virus] but you are still looking at the pool and asking if you can see anything new.

"And yes we did, which is why the vaccine recommendation for the northern hemisphere included a new H3N2 [flu] virus."

When a sample comes into the Francis Crick Institute, they first grow more of it - in small trays with a culture medium to encourage reproduction - so that there are plenty of samples to experiment with. On a scale of 1 to 4 (with 1 being low-risk infection such as E. coli and 4 being pathogens that can cause serious disease for which there is no treatment - and so must be worked on in a full biohazard suit), flu virus is a category 2, meaning the viruses must be worked on in a special biosafety cabinet.

The cabinet where Lynne Whittaker is working opens with a window that slides upwards.

She flicks a switch and there is a beeping sound - this means the protective air filter system is working. A wall of air then blows up and into a filter to try to stop stray virus blowing out into the room.

On the morning of our visit, she's working with red blood cells from ferrets that have been infected with known flu viruses and so contain antibodies - whether these antibodies lock on to the new virus or not will determine how much of a threat it might be.

Thankfully the newly shipped-in samples from China present no surprises - the antibodies in the ferret's blood attach to them. Once they have the initial results, assessing if it's a familiar subtype or not, the researchers conduct more in-depth tests looking at the genes of that virus to note any changes, for instance.

"Influenza is mutating all the time," explains Lynne Whittaker, "and you have to keep on it because it can be fast moving.

"When the flu season gets going in around December, right up until the vaccine meeting in February, we have to process as many viruses as we can - we may be analysing dozens of samples a day."

New strains could pop up anywhere - although they tend to emerge in places with high populations such as Bangladesh, says Dr McCauley.

If a new type of flu does turn up, the most important thing is to send samples of its genes to other surveillance centres so that they know what to watch for.

Some have questioned how open China was with sharing data about Covid-19, but Dr McCauley says he has no such concerns about flu.

"I get sent Chinese flu numbers every week," he says. "We have just received viruses from them to look at - there's no secrecy here."

Dr McCauley is on the fence about how bad this year's flu season will be, saying cases could rise due to low immunity. But "it's also possible that as there has been little flu around last year we are starting from a low level so cases just won't rise much", he says.

He stresses, however, that even if a vaccine is moderately effective it can make a big difference.

"If the vaccines are only 50 per cent efficient, that's 50 per cent less flu in the community and so that is a considerable benefit for healthcare - even 30 per cent is good and 20 per cent isn't to be sneezed at," says Dr McCauley.

"You are trying to ensure the hospitals can still function - and vaccination is cheap. A vaccine costs £20 - the alternative of having people in intensive care is phenomenally expensive."

Prof Easton believes it won't be such a catastrophic year.

"Historically, it takes about four years for the flu virus to mutate away the antibody protection offered by the infection or the vaccine," he says.

"So while you should get a new vaccine every year, the historical immunity [from previous years] you have will provide some degree of protection."

But we should not lose sight of the threat that flu poses.

"Flu is a dangerous virus - and I think we have become a bit relaxed about it," adds Prof Easton.

"There is every chance that a flu pandemic will come along that will be as devastating as the one that hit in 1918."

Dr McCauley adds: "The big concern is what happens when such a strain does spread - with a death rate that will make Covid look trivial."

Is he worried about being able to protect us? "We don't very often get this stuff wrong," he says, reassuringly. Let's hope for all our sakes that he is right.

© Daily Mail