19 Jun 2020
How do you test a vaccine?
Written by Professor Jodie McVernon.
This story is part of a special report prepared by University of Melbourne's Pursuit.
According to the World Health Organization, more than 120 COVID-19 vaccines have been proposed, of which at least six are in clinical trials.
But we need to remember that creating a vaccine is complex and difficult. Even when we have something that appears to work it takes time to establish that a vaccine is safe to use in humans and is actually effective in populations.
And there can be many failures along the way.
WATCH: It takes time to establish that a vaccine is safe in humans and is effective in the population. Video: University of Melbourne
For example, despite decades of work, we still haven’t produced vaccines for many diseases that researchers have focused on, like a vaccine for the HIV virus, or for the sore throat-causing Streptococcus-A bacteria that can go on to give rise to rheumatic fever and heart damage.
Neither do we yet have a universal vaccine for influenza.
That means new, or novel, strains of influenza can cause dangerous pandemics. The last time an influenza pandemic occurred was in 2009-10, when a new influenza virus emerged in Mexico. The one before that was the 1968 Hong Kong flu.
It just goes to show that is a persistent problem that we haven’t yet solved.
And safety has to be paramount.
We know that one of the previous unsuccessful attempts to create a vaccine for the SARS coronavirus appeared to make animal subjects more susceptible to severe infection.
Once a candidate for a viable vaccine has gone through laboratory and animal testing, it goes through a series of clinical human trials that will involve hundreds of participants and, when it comes to testing safety, ultimately thousands.
It is important to realise that in a disease like COVID-19 for which there are no therapies and can be fatal, no so-called ‘human challenge trials’ will be undertaken where vaccinated participants are deliberately infected with the pathogen to test the response.
Instead, the initial, or Phase 1 trial, will involve giving the vaccine to a randomly selected group of healthy individuals and then testing whether they produce the correct antibodies, in the required quantities, compared with those not given the vaccine.
This will establish whether the vaccine can generate the targeted immune response that is believed to be sufficient for protection.
A Phase 2 effectiveness trial will then test whether this response is consistent in more ‘real world’ settings across diverse populations – covering different ages, genders, medical backgrounds and pregnant women. They provide an early signal of common vaccine side effects.
Finally, in Phase 3, the vaccine is trialled in a larger population where the disease is present and participants are monitored for their results.
These trials are needed to prove that vaccine-induced immune responses are protective against infection or severe disease outcomes, and to detect any less frequent side effects.
The entire process involves ongoing safety checks before the vaccine can be approved.
There is an emerging assumption that we could have a COVID-19 vaccine within 12 to 18 months. It would seem implausible that a vaccine could come any earlier than that, given the urgency and the potential for simultaneous trials speeding up the process.
But, realistically, a vaccine could take years. That means we may for a time have to adapt to life with COVID-19, maintaining good personal and environmental hygiene, adopting physical distancing practices and continuing with public health measures including case isolation, and quarantine for contacts and travellers.
Perhaps the closest equivalent in living memory to what that could be like may be the periodic community outbreaks of polio before a vaccine was developed in the 1950s.
Developing a vaccine that can do a better job against a disease than our own immune systems is always incredibly challenging and can’t be taken for granted.