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Could this £2.50 gargle test developed in Cambridge be the solution to Covid-19 testing challenge?



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A rapid and cheap new gargle test that can diagnose Covid-19 has been developed that could hold the key to unlocking the government’s ‘moonshot’ goal of testing 500,000 people a day.

Working with a University of Cambridge laboratory, Professor Ray Iles has created a “game-changer” that resolves many of the issues experienced with the current coronavirus test.

Professor Ray Iles, of MAP Sciences, and son Jason working on the Covid test they have created. Picture: Keith Heppell
Professor Ray Iles, of MAP Sciences, and son Jason working on the Covid test they have created. Picture: Keith Heppell

He believes it could be rolled out globally, as the assay itself could cost a lab as little as £2.48 per sample.

The new technique – which has been shown to the UK government – has undergone testing with live samples, and can demonstrate whether the subject has Covid-19, influenza or a cold.

The test, relying on a type of mass spectrometry, begins with a person supplying a sample, simply by gargling with 10ml of tap water – a welcome alternative to the nose and throat swabs of the existing test.

“The existing Covid-19 test is not particularly pleasant, especially if you are testing children or having to do repeated sampling of a workforce. I hated it, and I can’t imagine having it done all the time,” Prof Iles tells the Cambridge Independent.

MALDI-ToF Mass Spectrometry test for SARS-CoV-2 .Picture: MAP Sciences. (42430593)
MALDI-ToF Mass Spectrometry test for SARS-CoV-2 .Picture: MAP Sciences. (42430593)

“A gargle is a great way to get to the back of the throat where an upper respiratory virus is found. We tried salt water and other things, but normal tap water works best.”

Gargle samples could be taken at home, at a testing centre, workplace or healthcare setting, then supplied to a lab for screening.

“We’ve worked out a safe way of handling it. If you’ve got a sample from someone with the disease, using UV light for 15 minutes will kill the genetic information – the viral RNA – but leave what we are looking for, which is the particle with the interesting proteins stuck on the outside,” explains Prof Iles, who is chief scientific officer at MAP Sciences in Bedford, which aims to commercialise the test.

“This is a nice, easy step and completely the opposite of what they do with the existing PCR test, because with that they want to preserve the genetic information, the RNA, but destroy the functional envelope and the proteins, hence they don’t do UV irradiation to neutralise it.”

Having made the samples safe, some lab processing is required.

“We pre-filter out any other bacteria, large cell debris or food, and we enrich our sample and concentrate down the viruses that might be in your gargle. This is the acetone step. It does everything we want and it’s cheap – which is important so that all countries can use this technology,” says Prof Iles. “Simply by doing an acetone precipitation at one-to-one, you bring down all the massive viral particles and some very big antibodies down as well, but all the other proteins are cleared.

“What you are left with is a pellet which is enriched with the virus and any other big proteins, such as the immunoglobulin A (IgA) antibodies, which are the major barrier to the infection getting into your body.

“The acetone also deforms the virus, so if we haven’t killed it with the UV light, it is absolutely non-functional after the acetone.”

Having prepared the sample, it is placed in a mass spectrometer – machines that are widely used in chemistry and bioscience to analyse the mass-to-charge ratio of molecules, producing a distinctive bar chart-like fingerprint.

“These are not normal mass spectrometers that we use. These are matrix-assisted laser desorption/ionisation, or MALDI, mass spectrometers. This will ‘soft ionise’ your proteins, so that they have one or maybe two charges and they can separate in the mass spec, according to their molecular mass.

“These proteins are big – up to 250,000 daltons,” says Prof Iles, who lives in Ely.

One of the most significant achievements of the team working on this was to find a way to release the distinctive proteins, such as the spike protein, without skewing the results.

“We have a magic formula with our dissolution buffer, which gets the proteins out from the viral envelope membrane but doesn’t interfere with the mass spec,” explains Prof Iles, who is a visiting research professor at the University of Cambridge, working with the Laboratory of Viral Zoonotics.

“We also make sure the viral proteins are of a size, by breaking disulphide bonds, that are still characteristically large so that they can be seen in the mass spec.

“When we run it in the mass spectrometer, we’ll get a distinctive pattern. We see all the viral envelope proteins and then our distinctive coronavirus virus protein – the S1 fragment of the spike protein. We do detect the others as well, although they’re not as easy to see. But the S1 is extremely characteristic of the coronaviruses.

“We are seeing other coronaviruses as well, but we’re finding other distinguishing markers of Covid-19. It’s a fantastic first screen.”

Prof Iles suggests the test could be run quickly, cheaply and regularly to rule out Covid-19, or indicate its presence. Further more specific PCR testing could then be carried out if required on those who test positive.

“We also pick up the immune response as well. This was a real bonus,” he notes. “We definitely pick up the IgA immunoglobulin protein as it’s broken, so we can measure the magnitude of the IgA immune response. This tends to be viral specific – if you have a viral infection, you’ll have an IgA response.”

While such a response could be prompted by another virus, it would not coincide with the presence of an S1 spike protein.

“Another added bonus is that we can tell if you have an immune response, and that you have viral proteins, even when it’s not coronavirus – and we can tell you what the other viruses are. We can tell you if it’s influenza or if it’s a cold virus. They are quite distinctive different proteins we’re picking up.

Professor Ray Iles of MAP Sciences and son Jason (left) working on the Covid test they have created. Picture: Keith Heppell. (42428544)
Professor Ray Iles of MAP Sciences and son Jason (left) working on the Covid test they have created. Picture: Keith Heppell. (42428544)

“This is a major advance. Suddenly, we can tell you if it’s rhinovirus particles – meaning a common cold – or influenza and distinguish those from coronavirus.

“We are refining it so we can definitely distinguish from Covid-19 and seasonal coronavirus. We’re tending to find the seasonal coronavirus has much lower spike levels.”

Major benefits of the test are price and speed – two factors critical to scaling up global testing to the levels required.

“This is so much cheaper and so much faster than the existing PCR [polymerase chain reaction] test,” says Prof Iles. “The laboratory cost is £2.43. The reagent cost alone for PCR is £30 at least. The price and speed at which you can do this means you can do this as a first-stage mass screen. Positives could be checked with more specific PCR tests, so the pressure on the PCR facilities would drop tremendously. You have a well-designed screening strategy.”

It could help eliminate the problem of identifying false positives.

“There are a lot of people out there being taken out of the workforce. You could monitor them every day if you wanted and get them back to work,” says Prof Iles. “It’s the game-changer that we’ve been advocating.

“The weak point is poorer countries. There will always be a reservoir of this coming back. This is our motivation. You have to look globally, so we can provide frontline screening technology for the world, not just the rich nations.

“You can do a batch preparation with everything set up in 45 minutes. Then from receiving the gargle sample, we can turn out the result in an hour.”

The acetone step in the MALDI-ToF mass spectrometry test for SARS-CoV-2. Picture: MAP Sciences
The acetone step in the MALDI-ToF mass spectrometry test for SARS-CoV-2. Picture: MAP Sciences

The team has been cautious in speeding up the tests to ensure good results, but it could be possible to speed it up further by taking fewer ‘shots’ in the mass spectrometer.

The team – which has also worked with the Royal Papworth Hospital, the University of Kent and Northern Illinois University on the test – has carried out extensive testing to find the ‘failure’ point of the machines used to understand the scalability of the method.

“We’ve pushed the mass spec machines to the limit so we know the point at which they fail. Your need to do some preventative maintenance by getting in and cleaning the primary lens,” explains Prof Iles.

Some mass spectrometry machines offer easier access than others to this primary lens, such as the desktop MALDI-8020 from Shimadzu, which Prof Iles and his team have been using. But are there enough of these machines already in place?

“There are not enough in the country at the moment, but Shimadzu says it could have 150-200 by May of this model. Then they could grow.

“There are other machines with access to the primary lens.

“We’ve developed the buffer, the quality controls, the whole system of monitoring and know the result is good for this one, but we can do it for other machines – it’s just time and money.”

And that, at the moment, is proving to be the barrier to scaling this exciting breakthrough technology.

“The government have reviewed this, but if I’m honest, they are slow and we haven’t had any funding from them,” says Prof Iles. “We want people to see the work we’re doing. This has all been done by our own people, with no government funding.”

With tests being carried out on other machines at the University of Illinois, Prof Iles is hopeful of securing approval for the test from the US regulator, the Food and Drug Administration (FDA).

The results of the mass spectrometry test. The peak at S1 shows the presence of the viral S1 spike protein, while the IgA peak shows the immune response picked up on the test. Picture: MAP Sciences
The results of the mass spectrometry test. The peak at S1 shows the presence of the viral S1 spike protein, while the IgA peak shows the immune response picked up on the test. Picture: MAP Sciences

Frustratingly, for a machine developed in the UK, he thinks approval here could take longer.

“We are commercialising this through MAP Sciences but we’ll work with any partners. Our philosophy is we want to bring rapid, affordable diagnostic testing. It’s not about milking people,” he says.

Prof Iles believes an investment of £5million-£10million is required to scale the diagnostic test, which is being called v-SCREEN. It represents a drop in the ocean compared to the billions being spent on Covid-19.

The progress to date has relied heavily on the work of Prof Iles’ colleagues in Cambridge, notably Prof Jonathan Heeney , head of the Laboratory of Viral Zoonotics and founder of its spinout DIOSynVax, which has had £1.9million backing to carry out clinical trials of the potential Covid-19 vaccine he has developed, as the Cambridge Independent reported in August.

“We were introduced to Jonathan because we’d developed this technology for other applications – haemoglobin disease, sickle cell disease, screening entire populations for blood disorders,” says Prof Iles. “The whole rationale of the design was to make it really feasible for mass screening. The test for haemoglobinopathies was a pinprick blood test, because we knew people could do that at home. Make it easy!

Professor Jonathan Heeney is head of The Laboratory of Viral Zoonotics at Cambridge. Picture: Keith Heppell
Professor Jonathan Heeney is head of The Laboratory of Viral Zoonotics at Cambridge. Picture: Keith Heppell

“We had always wanted to work on the virus but I didn’t have a category three facility. Jonathan was absolutely fantastic. He knew what we needed was to work on ‘pseudoviruses’ because they are safe.

“They were the model for us to build the diagnostic on and once we’d built it on the pseudotypes that he and colleagues in Kent had developed, then we could move to the live virus.”

The Laboratory of Viral Zoonotics’ category three labs enabled this to be done safely.

“Without Jonathan, we couldn’t have done this. Now he’s got me looking at antibody responses.”

Among those who also helped was Prof Iles’ son, Jason.

“He works at Cambridge and worked for nothing for us to get this up and running in the early days and is still working on it,” he said.

“It’s such an interdisciplinary collaboration. We’ve got engineers, chemists, mass spectrometrists, biologists – the whole lot.”


Read more

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University of Cambridge’s Prof Jonathan Heeney answers call from Bill Gates to transform flu vaccine

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