QUB professor on the struggle to find a vaccine
Queen’s expert tells of difficulties in tackling a largely unknown virus
FOR scientists everywhere, it is the mission of their lives. In labs around the globe they are racing against time in a frantic bid to create a Covid-19 vaccine — seen as the key to vanquishing the virus and setting society on the road back to normality.
The world is waiting, hoping, expecting, but it is a pressure to deliver that weighs heavily on the shoulders of the scientific world.
It is said the best way to tackle an enemy is to understand how that enemy operates, and that is why understanding the nature of Covid-19 is vital.
“The problem is, this is still a very new virus,” said Dr Ultan Power, professor in molecular virology at Queen’s University.
“We have learnt so much about it in such a short space of time, it’s quite remarkable. But there’s still a lot more to find out.
“We know the virus does not have the ability to mutate in the way influenza changes. It’s not as dramatic as that, but this is still a new virus as it’s only been around for a few months. We still don’t know what it will look like in one or two years’ time. That’s an issue to begin with.”
The simplest way to imagine Covid-19 is as a tiny tennis ball with ‘spikes’ around the surface, which are formed by proteins.
Those spikes interact with another protein on the surface of the human cell called the ACE 2 Receptor.
The spikes help the virus to roll along the cell until it comes across this receptor.
The ACE 2 Receptor is the lock, the spike protein is the key. Connection allows the virus to enter the cell using viral RNA, and that is the most important part of the virus. It effectively acts like a photocopier.
RNA manages how the other parts of the cell function. When the virus RNA gets into the cell, it reassigns everything to one job — make more virus particles.
Instead of the cell doing things to keep our bodies working efficiently, it focuses on making viruses. One gets in, thousands of virus particles come out. They infect other cells, and eventually other people. That process happens over and over again, and very suddenly — in just a few weeks — you have a global pandemic.
The human immune system reacts to defend the body, but for some people the immune system is overwhelmed. Overactive, it causes damage to tissue and organs. Lungs may be unable to operate. The weaker the immune system in a person, the more likely serious damage is caused, hence the shielding of those most vulnerable in our society.
A lot of the drugs — antivirals — being trialled and tested across the world are trying to stop this viral replication.
A vaccine is seen as the game-changer, the route back to the world we knew.
Vaccines teach your immune system how to create antibodies that protect you from diseases.
Having a vaccine also benefits the whole community through “herd immunity”.
If enough people are vaccinated, it is harder for the disease to spread to those people who cannot have vaccines.
Anthony Fauci (right), the face of America’s fight against coronavirus, believes a vaccine may be ready in 12 to 18 months.
It sounds a long time, but history shows it really isn’t.
Fauci’s timeline would shatter all precedents for developing a new vaccine, which can take many years. The fastest vaccine was for mumps, and took four years.
Optimism about an Aids vaccine was once high, but 40 years later we still wait.
Dr Power added: “Unfortunately, no one is going to be sitting in a laboratory and waving a magic wand and suddenly saying there’s your vaccine. It’s a much more complicated process than that.
“There are around 70 vaccines in clinic at the minute, most of them targeting the ‘spike’ protein, which latches itself on to the cells.
“If that can be nulled then the virus can’t latch onto the cells and cannot become active and infect.
“But there’s no one definitive process on how to develop the vaccine in the first place, and that’s before you get to the testing stage.”
Some of the candidate vaccines involve hugely weakening the virus, before putting it into the body. The idea is to stimulate the immune system to create enough of the right type of antibodies to be ready to fight the real thing. Others involve finding a way to get a virus particle that our systems can easily fight off, and get that to carry the spike protein from SARS-COV2, the virus that causes Covid-19. The idea being our cells which make antibodies will learn to recognise the shape of the spike protein, and be ready to stop it entering the ACE-2 receptor (the lock) when it arrives on the real virus particle.
At Oxford University Irish Professor Adrian Hill is heading a team using this method, the current leaders in the race to develop a vaccine to stop the virus.
And a final truly modern method is being worked on by several companies, including Usbased Moderna.
It involves cutting up the RNA
❝ But in everything we do we can’t lose sight of the fact that we must always follow the data
of the virus, effectively clipping up the page before it is put into the photocopier. The aim of this is to isolate the bit of the virus RNA that makes the spike protein, and get that into our cells.
Our cell machinery will then ‘photocopy’ the spike protein, but never see the rest of the virus particle. Those spikes will be recognised by the immune system, which will make antibodies, ready for a time when the spikes arrive on the virus particle.
These are known as RNA vaccines, and many experts believe they will be key to fighting infectious diseases in the years to come, but the technology to produce them has only become viable in the last few years, and none have yet been rolled out.
Once approved, they would be very quick to produce, but testing of such designs — and all designs — would be crucial. Dr
Power explained: “It’s very difficult to say what the best method is and the construction of the vaccine is critical.
“And we have to remember our primary targets are the elderly and they are much more difficult to vaccinate than younger people as their immune system is weaker.
“But once the method of production of the virus is settled, the next step is to scale up to a level where you can produce millions of doses.
“Then it’s a case of repetitive testing through several phases, with safety the main issue throughout the whole process.
“With pre-clinic trials, perhaps involving mice, you allow the virus effect to be minimal but we can determine the capability of immune response toxicity levels, whether the vaccine does too much damage to be useful.”
If the vaccine gets through that stage, then it is on to testing in a clinic. But, as Dr Power explains, many hurdles still lie ahead.
He added: “Safety is again the key, making sure there are no problems caused, watching the consequences and toxicity levels. Any signs of toxicity and a decision will have to be made on whether to progress to the next phase.
“That’s when you introduce the vaccine to a series of trials with a limited number of subjects, again ensuring safety all the way through. You look for dose effects, how much of the potential vaccine produces the best results. Then you select the dose to proceed with to another stage.
“Using a much greater number of people, perhaps thousands, there must be a robust response. If everything comes together and the vaccine still produces positive results then the steps to authorise can start.
“A decision will be made whether to manufacture or not and all the details in the dossier will be looked at before a licence to produce is granted.”
It all sounds like a lot of work, and it is.
“With this pandemic there is a lot more pressure to produce and there’s a temptation to relax a little in terms of vigilance,” said Dr Power.
“But you must be sure any vaccine will not cause more damage. Normally the whole process takes around 10 years.
“I spent nine years working on a vaccine and it fell at the third stage. It’s not easy, there’s a lot that can go wrong. And even if the vaccine does work, can we be sure it will still work in a year’s time?
“You normally need at least a year to monitor that, take time to draw breath and then move to the next step. If there’s anything viable within the next 18 months we’re talking about history book stuff.
“By the end of this year we might have a candidate, but it’s too critical to rush through.” There can then still be issue if any vaccine is brought to market, Dr Power explains.
Problems can develop, a one in a million reaction can be missed.
He added: “It’s wonderful to see the aspiration to produce a vaccine for Covid-19, but the pressure of your country is not what you want on your shoulders, especially if things go wrong down the line.
“We all want this so badly there’s a real danger of problems. We have to work out which specific people have a bad reaction — that’s normal with any vaccine.
“There’s a risk with everything and those risks will be found out in trying to gain approval to bring to market.
“The risks must be balanced. Those people who have a reaction will then not be given the vaccine and the theory is that herd immunity protects them. The virus struggles to find those without vaccination. The majority protect the few.”
He added: “But in everything we do we can’t lose sight of the fact that we must always follow the data. That takes a considerable amount of time.”