Professor Graham Le Gros

International Day of Immunology 2020: When a virus and the immune system collide

29 April 2020, COVID-19, Immune system, International Day of Immunology

When the immune system encounters a new virus, it immediately launches a response to fight it. The type of response is important. You don’t want a lack-lustre fizzle – but neither do you want to recreate the big bang. Neither help to get rid of the virus.

As we mark International Day of Immunology and with global focus on COVID-19, Professor Graham Le Gros, Director of the Malaghan Institute of Medical Research, explains some of the different strategies viruses use to evade or outpace our immune system, and what’s needed for us to find a cure when a new infectious agent arrives on the scene. 

Viruses big and small

Viruses are among the simplest infectious agents, but they can be the most deadly. While things like bacteria and parasites seek us out for protection and shelter, viruses need us purely to replicate – to create more copies of themselves.

“There are different types of viruses,” says Prof Le Gros. “Larger ones tend to dwell inside the genetic material of our cells, where they can hide undetected for years, but smaller ones opt to get in and out of cells as quickly as possible, replicating as many copies as they can in the shortest amount of time.

“Smaller viruses, like the flu, hang out inside our fluids like mucus and blood. They are designed to replicate quickly and are highly mutative to constantly stay one step ahead of the immune system,” he says.

“As far as we know, SARS-CoV-2, the virus which causes COVID-19, presents itself in a way similar to the influenza virus, quickly replicating, generating thousands of copies. But unlike the flu, SARS-CoV-2 is capable of infecting many different parts of the body – the brain, the lung, the gut. There are still big questions we need to answer about this virus before we can find a cure.”

What’s key to finding a cure?

To find a cure, first you need to understand the virus, says Prof Le Gros. Where does it go to in the body? Does it hang out in fluids or does it hide in cells? What’s its Achilles’ heel? These are the questions we must answer before even considering a vaccine.

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The next step is understanding how harmful, or virulent, the virus is. That requires looking at its DNA and understanding what genetic components it has that relate to disease. Does it stimulate immune-suppressive qualities? How does it spread from cell to cell? How transmissible is it between people? Looking at the virus’s genes helps scientists understand the severity of the virus and what sort of risk it poses to the population.

Once we know how virulent a virus is, its behaviour and where it’s found in the body, we can then design a vaccine by creating antibodies specific to this virus.

However, antibodies alone aren’t necessarily enough to stimulate an appropriate immune response. This is where the “immunologist’s trick” comes into play, explains Prof Le Gros. By adding what is known as an adjuvant to the mix, the immune response can be skewed one way or another. This is the key that turns an antibody into a cure.

Like sleight of hand, adding an adjuvant into the vaccine mix nuances the immune response in the proper direction. Adjuvants can be a lot of things – chemical compounds, proteins, even bits of dead virus. The art of adding the right adjuvant, or adjuvants, to the mix is where immunologists transform a weak response to a viral-killing powerhouse. Conversely, adding the wrong adjuvant could be catastrophic, stimulating a deadly storm of toxic immune cells and molecules that have the potential to kill an individual.

What’s needed to develop a COVID-19 vaccine

Understanding how to assist the immune system safely against the SARS-CoV-2 virus is where the attention of research around the world is focused, says Prof Le Gros.

“When it comes to COVID-19, we don’t yet know enough about it to confidently pick the appropriate immune response.

“We’re aware of ways we can stimulate immune responses to SARS-CoV-2, but even getting it slightly wrong can lead to fatal consequences. It’s not necessarily a case of ‘not enough’ in terms of stimulating an immune response, you can have too much of an immune response and people can die from an overreaction.”

Therefore, in the effort to finding a cure, and manufacturing a successful vaccine – or more likely, vaccines, there is no such thing as too many cooks in the kitchen, says Prof Le Gros.

“The more people we have studying this thing, bringing it into the light and finding all its tricks and ways it escapes the immune system, the better. 

“It’s essential that research, pharma and government come together not just within their own national borders, but internationally. The more collaboration, the quicker we understand this virus and the sooner we get back to ‘normal’ life.”

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