Our director Rob Field was invited to write a thoughtleader for MedTech Innovation News on the subject of the use of glycoscience in viral surveillance and pandemic preparedness

Reproduced with thanks to MedTech Innovations News:

Prof Field wrote:

With the world still battling coronavirus and focused on the Omicron variant, the World Organization for Animal Health (the Office Internationale des Épizooties – OIE) has been urging countries to increase surveillance for avian influenza following outbreaks of the virus across 41 countries in Europe, Asia and Africa (including the UK, France, Poland, Russia, Israel, Japan, and China) over the last six months.

It is the “unprecedented genetic variability of the H5N1, H5N3, H5N4, H5N5, H5N6 and H5N8 subtypes of high pathogenicity avian influenza (HPAI)” circulating in bird and poultry populations across the globe, which has sparked such concern at OIE, for creating what’s described as “an epidemiologically challenging landscape”.

In October alone, there were close to 16,000 cases of HPAI reported, signalling an increased risk of virus circulation. However, it is the increase in human infections caused by the H5N6 subtype of avian influenza – one that causes high mortality – which is causing most concern amongst experts, who say that the subtype appears to have changed and could now be more infectious to people. Since the first infection of a human in China in 2014, there have been 51 cases of human infections caused by this H5N6 subtype – half of which have been reportedthis year [according to the US Centers for Disease Control and Prevention (CDC)].

If we have learned anything from the coronavirus pandemic, it’s that we have the skills to produce diagnostics, vaccines and therapeutics in record time to combat viruses that cross-species jump and threaten our lives. The Coalition for Epidemic Preparedness Innovations (CEPI) has set the benchmark at 100 days to develop vaccines in a bid to redress and prevent future pandemics.

However, it is the area of viral surveillance – spotting potentially deadly viruses early – that is fast becoming the mainstay of ‘pandemic preparedness’ and our future protection policy. Early detection of viral hybrids capable of cross-species jumps or deadly mutant variants can limit the spread of these viruses and can be the difference in a disease escalating from an outbreak to an epidemic and then to a pandemic.

In this area, Iceni Diagnostics is exploiting a novel glycoscience-based approach which relies on sugars (carbohydrates) found on cells in the body. Viral infections frequently start through the interaction of the virus with sugars on the surface of cells. Since there are multiple types of sugars on the cells, specific viruses tend to interact with specific sugars. In the case of avian influenza, the H5 component of the virus interacts with a different sugar than a typical human virus (H3 for example). The problem arises when hybrid viruses containing components of both avian and human influenza naturally form. It is these viruses that are particular threats to humans because they are abnormal and capable of cross-species jumps (zoonotic outbreaks) such as was seen with the swine influenza pandemic of 2009 – and, unsurprisingly, they are now underpinning a whole new generation of viral surveillance.

From a public health perspective, it is critical to identify aberrant viruses as early as possible. Fortunately, the sugars that are involved in this process have been identified and using the specialist technology that Iceni Diagnostics offer can be used in routine epidemiologic screening, therefore providing an early warning of a potential threats caused by mutant and hybrid viruses that pose a bigger risk to the human population.

In a normal viral infection, you have a cell coated with surface sugars which the virus attaches to. Iceni Diagnostics has replaced the cell with something much smaller (gold particles for convenience) and has mimicked the cell surface, displaying the sugars so that the virus sees something that looks like a cell surface and can bind to the relevant sugar.

Given that sugar binding is essential for most respiratory viruses to infect, and that specific viruses only bind to certain sugars in the body, exploiting the presence of these sugars enables the Iceni Diagnostics’ test to easily spot viruses that can jump species, as well as detect and discriminate between different variants of known viruses and even identify as yet unknown potentially killer viruses in a single test.

In terms of early surveillance, by working uniquely at the initial binding stage of a virus, glycoscience enables us to achieve an extremely early result – picking up on new variants or hybrids far quicker than other tests which typically work by detecting viral nucleic acids (eg PCR tests) or proteins (antibody-based tests), both of which require prior knowledge about the virus.

Even with viruses that more commonly affect us, such as seasonal influenza, this carbohydrate-based approach is beneficial, some would say essential. Lest we forget, pre-coronavirus and during the three combined influenza seasons of 2015 – 2018, seasonal influenza killed 44,505 people in England alone.

Indeed, seasonal influenza is more complicated than it may first appear, and it could prove extremely serious for us, now that lockdown has been lifted, without surveillance to know what we are dealing with.

To begin with, we know of several different subtypes of influenza currently circulating. The one that normally affects humans (H3N2) predominates, but swine influenza (H1N1) and the more common avian influenza (H5N1) are also prevalent.

As with all viruses, influenza, irrespective of subtypes, cannot reproduce independently. Its life cycle involves binding to the sugars (carbohydrates) in the host body so that it can enter cells, where it reproduces and infects other cells in the vicinity. However, it must infect human or animal cells and use the host cellular machinery in order to replicate before it can burst free and move on.

An avian influenza subtype binds to avian sugars which are slightly different to human sugars. It doesn’t ordinarily infect humans. However, the life-cycle of influenza viruses means that avian, swine and human viruses can mix to produce hybrid viruses which can infect human cells via binding to human sugars. As noted above with the H5N6 subtype, it is when hybridisation and mutation occurs that things can get really nasty because humans are not routinely exposed to avian influenza, and so they respond badly to it.

Although the adoption of glycoscience in ‘surveillance work’ is something new, application of glycoscience to diseases and the use of sugars in diagnostics and therapeutics has already been clearly demonstrated. The GlaxoSmithKline anti-viral influenza treatment, zanamivir, for example, (better known by the trade name, Relenza), is a sugar (carbohydrate) mimic, and has been in use for more than a decade. Relenza doesn’t stop the virus from binding or replicating. But it works at a later stage in a virus’ life cycle, blocking its escape from the host cells and preventing its growth. The virus is held onto by the host cells, giving the immune system time to attack and destroy it.

It’s not only humans, chickens and pigs that can be infected by influenza, horses, dogs and cats are all hosts for the virus too. This obviously has veterinary implications. More recently, a study by Iceni Diagnostics, relying on sugars to specifically detect the equine influenza H3N8 virus and all variants thereof, has demonstrated its capabilities in veterinary viral surveillance quite convincingly.

Researchers at Iceni Diagnostics tested sugar binding using a viral vaccine consisting of two or three inactivated equine influenza viruses (including equine influenza virus H7N7, which is more or less extinct in the world now, as well as the prevalent H3N8 and a number of other purified laboratory type viruses which no longer naturally occur). The carbohydrate-based test didn’t detect the H7N7 but it did identify the H3N8 and all variants of it from all over the world. This is a good proof of principle which highlights the potential this test has in detecting emerging variants of H3N8 before they have even been isolated and characterised. And we can now say, without fear of contradiction, that this test will detect all known antigenic and genetic variants of H3N8. This method of surveillance is going to have huge impact for both humans and animals in the future.