The race is on to develop a vaccine that will guard against the COVID-19 pandemic.
But don’t expect it to be played out as a quick dash to the finish line. More than likely, it will be a long and difficult marathon with an uncertain outcome.
“Science cannot be rushed,” says Rob Kozak, a clinical microbiologist at Sunnybrook Health Sciences Centre in Toronto.
He notes that researchers must follow well-established regulatory protocols that are designed to ensure a new therapy is both effective and safe.
The purpose of a vaccine is to expose the body’s immune system to some portion of the virus so it can prepare in advance for a real attack.
For instance, a vaccine might include an antigen, or protein, from the surface of the virus. But finding the right antigen that will trigger an effective immune response is easier said than done.
Viruses are constantly mutating and evolving. The strain of a virus circulating in Canada might be slightly different from one in China or Europe. This means the antigen must produce immunity against all strains, or variants, of the virus.
Once an antigen is selected, it has to be tested in animals before human trials can begin. Finding the appropriate animal model also presents challenges. The animal needs to respond to the virus – and the vaccine – in the same way as people.
Fortunately, researchers can look to previous vaccine studies for some clues on how to respond to the current pandemic.
The COVID-19 illness is caused by a coronavirus, officially known as SARS-CoV-2.
Coronaviruses are a family of viruses that produce respiratory symptoms ranging from the common cold to serious breathing problems.
In recent years, humanity has been challenged by two other deadly coronaviruses – Severe Acute Respiratory Syndrome (SARS) in 2003 and Middle East Respiratory Syndrome (MERS) in 2012.
During both these outbreaks, researchers started to develop vaccines. In the case of SARS, the work was never completed partly because it ceased to pose an immediate health threat. SARS seems to have morphed and mysteriously disappeared. MERS vaccine trials are ongoing.
Data gathered in those initial efforts are helping to guide some aspects of COVID-19 vaccine development – including selecting appropriate animal models and viral targets.
One potential target is the part of the coronavirus that latches onto human cells.
“If you have ever seen images of a coronavirus, you will have noticed that it has spikes,” explains Kozak, who is a member of one of the Canadian teams racing to develop a vaccine.
“Those spikes are what the virus uses to attach onto your cells. They are excellent targets because if your antibodies (part of the immune system’s defences) bind to them, the virus isn’t going to be able to enter the cell and that is the first step to defeating it.”
Furthermore, the spikes, which are made of glycoproteins, are likely to remain fairly stable. “If the spikes change too much, then the coronavirus won’t be able to get into human cells,” says Kozak.
Previous SARS research also reinforces the importance of doing thorough testing in animal models before any potential vaccine is given to human volunteers.
In one study, an experimental SARS vaccine actually made lab animals worse, says Arinjay Banerjee, an emerging viruses researcher at McMaster University in Hamilton.
“This study showed that when mice were vaccinated and then challenged with the pathogen, there was an enhancement of the infection,” he says.
“The vaccinated mice developed disease more rapidly and died more rapidly than the unvaccinated mice.”
Another study revealed that some investigational SARS vaccines produced negative side effects in some types of animals (such as ferrets) but not in others (such as mice).
For that reason, many researchers are firmly convinced that a vaccine should be tested in two different types of animals, says Kozak.
All this pre-clinical work is time consuming. Laboratory animals require specific time periods to develop a response to the vaccine and to then react to the virus. The clock can’t be made to run faster, says Kozak. And if an experimental vaccine fails, a research team could find itself again at the starting gate.
“There is a lot of back and forth that can happen while making a vaccine,” says Banerjee. “It’s a rigorous process.”
After a vaccine has successfully passed animal testing, it is then tried in a relatively small group of healthy volunteers. This is known as a phase one clinical trial. It’s basically a safety check to make sure the vaccine doesn’t cause serious side effects.
If the vaccine clears this critical hurdle, trials are gradually expanded to include more people who are observed for longer periods of time in order to gain a better understanding of a vaccine’s risks and benefits.
Meanwhile, scientists are already exploring various ways to deliver a COVID-19 vaccine.
One U.S. team is considering using messenger RNA (mRNA) which would rely on the machinery of the body’s own cells to produce a virus protein. The mRNA essentially provides the instructions for making the protein. It’s hoped that the presence of a viral protein will prompt the immune system to produce antibodies and marshal other resources against the coronavirus.
Another group is considering a slightly different method using synthetic DNA.
These genetic approaches received a kick start in February when a Chinese laboratory sequenced the SARS-CoV-2 genome – or the microbe’s genetic blueprint – and then published the findings for all to see.
Still other scientists are toying with different innovations, including growing virus-like particles in plants to bolster vaccine production.
“Each of them have their advantages and disadvantages” in terms of the ease and speed of vaccine development, says Kozak.
“To be honest, I don’t think we are going to have just one vaccine,” he adds. “In fact, I hope we don’t. I hope we have three or four amazing candidates that all work basically as well as each other, and that could be critically important because you don’t want to be dependent on only one company to provide for the world.”
So, how long will it take to develop a vaccine? Between one and two years, estimates Kozak.
And once a vaccine does exist, special production facilities will have to gear up operations to meet the global demand. That, too, will take time.
That means a “quick fix” vaccine isn’t on the immediate horizon. To make matters worse, there are no medicines that have been proven to help the body fight the virus.
It’s possible that doctors might be able to repurpose some anti-viral drugs and related therapies that have already been approved for other conditions, says Dr. Banerjee. But before they are routinely administered to COVID-19 patients, the drugs need to be properly tested to make sure they don’t do more harm than good, he adds.
Given all these factors, what’s the bottom line? If you really want to protect yourself from being infected, follow the advice you’ve heard repeatedly from public-health officials – frequently wash your hands, don’t touch your face, and maintain a physical distance of at least two metres away from other people when venturing into public places.