Scientists worldwide are searching for potential COVID-19 vaccines, but they’re far from easy to make, and would normally take years to become available. Professor Colin Pouton unravels the challenges of finding a swift answer.
As COVID-19 restrictions ease, medical scientists across the globe are searching for potential vaccines against the deadly virus. Experts agree that dangerous respiratory illnesses – and, potentially, future pandemics – are likely. Vaccines are complex to make, with most taking 10 to 15 years and three phases of testing to enter the market.
Here, we ask Professor Colin Pouton from Monash University’s Faculty of Pharmacy and Pharmaceutical Sciences about the virus itself, and the challenges of quickly finding a vaccine.
A serious global pandemic of a new virus – while deadly serious – must be fascinating for research pharmacists. What’s captured your attention most about COVID-19?
COVID-19 illustrates how viral infections caused by closely related viruses can have very different characteristics. The COVID-19 virus (SARS-CoV-2) has a similar structure to the SARS coronavirus, but COVID-19 presents very different problems. SARS-CoV-2 is much more contagious, but isn’t as life-threatening. SARS was contained because it was easy to identify infected patients, and the risk of catching SARS was low.
Many people experience mild symptoms when they catch COVID-19, so we have very little idea how many people have been exposed to the virus. Until we start testing large numbers of people, irrespective of whether they’ve experienced COVID-19 symptoms, we will not know the scale of the problem we’re facing. Some reports suggest the actual number of infections may be 20 times higher than the published figures. That would be good – we would be further down the path to “herd immunity”.
Human trials have already started on some potential vaccines. Can you talk us through what’s been happening since March?
There’ll be several different approaches to vaccination in human safety trials by the end of June. The announcements are coming thick and fast. The consensus is that all approaches are worthy of investigation at this stage. Most programs will probably progress to small efficacy studies if they have sufficient funding.
What’s not clear at present is how large a phase III efficacy study will be required. This is why there are so many conflicting opinions on how long it will take. The desire to find a vaccine quickly will encourage some fast-track approaches with the agreement of regulatory agencies
What’s your faculty doing, specifically, around developing a vaccine?
We think mRNA vaccination is the most promising way to respond quickly to an outbreak such as COVID-19. Over the past few years, we’ve been working on mRNA delivery for both vaccination and therapeutic applications, so it was natural for us to make some candidate COVID-19 vaccines.
There are three or four well-funded international programs making use of mRNA technology, one of which was the first vaccine to enter clinical trials, a US program involving Moderna Inc and NIAID (part of NIH).
These programs are unlikely to publish the details of what they’re doing. So, our immediate interests are to investigate how to optimise the design of the mRNA molecule and the design of the delivery systems. We’re testing our vaccine candidates at present. We’d be very interested to take an Australian mRNA vaccine forward into the clinic, but this will depend on funding.
What is mRNA technology? Is it a new class of drug? What’s new about it?
Yes – mRNA is effectively a new class of drug, and as yet there are no products approved for human use. It’s likely that a COVID-19 vaccine will be the first mRNA product. Messenger RNA (mRNA) molecules encode for production of proteins. They’re produced from DNA in the cell nucleus, and are exported into the cell cytoplasm, where they take part in the process called “translation” – that is, the code is used to guide production of a specific protein.
One of the interesting aspects of COVID-19 is that it’s so contagious that it should be much quicker to set up test and control groups and establish efficacy.
When we inject an mRNA vaccine, the mRNA gains access to cells, and is then translated to produce a viral protein, or part of a viral protein. In the case of COVID-19, we’ll deliver an mRNA molecule that encodes for production of the SARS-CoV-2 spike protein, or a fragment of the spike protein. The hope is that this will allow our immune systems to raise antibodies against the spike protein that will neutralise the virus and prevent infection.
There’s already been reports the virus has mutated. Does using this mRNA technology mean you respond to changes quickly – and swifter than other research teams?
The mutations we’re hearing about are small changes that aren’t causing significant changes to the activity of the virus. RNA viruses typically mutate regularly, but the COVID-19 virus, as with other coronaviruses, is relatively stable – which is a good thing in relation to developing a vaccine.
Large changes that occur and change the properties of the virus – such as SARS to SARS-CoV-2 – are much rarer events and usually involve substantial change in the viral genome, such as acquisition of a piece of RNA from another virus. When a large change occurs, it usually implies the need for a completely new vaccine and – yes – mRNA technology would be a great way to respond quickly.
We think it’s important that Australia develops capability and capacity in mRNA technology. This would allow us to respond rapidly to the next viral challenge. This would be particularly important if it happens to be a local event in our region of the world.