Next, we move on to the clinical trial stage, where in Phase I the vaccine candidate is tested in a small group of people (about 20 to 30) to ensure safety, followed by Phase II, where a larger group of individuals (typically hundreds to thousands) is tested for safety, dosage, and administration.
Finally, in Phase III the manufacturer would test the vaccine on thousands of people and look for the incidence of disease in their large sample. It takes time to recruit people, find sites for clinical trials, and establish protocols. Once all that is done, these large vaccine trials can go on for anywhere between one to five years, because you are waiting to see if your vaccinated group has a lower incidence of disease than your placebo group.
Again, given the urgency of this situation, a surrogate endpoint may be used such that the effectiveness of the vaccine is measured in the type and length of immune response it can elicit. But even then, you’re talking one to two years for this last phase alone. Also, one must remember that there is a high failure rate at each stage, so just because we found an antigen at the exploratory phase doesn’t mean it will end up being a vaccine.
Another important aspect is scaling and manufacturing. Regulatory approval does not mean that enough vaccines can be manufactured quickly enough and then be available for the entire population. We often have flu vaccine shortages, even after planning those vaccines in advance.
Is it correct that a coronavirus vaccine has never been developed? And if that’s so, why wasn’t one developed after the MERS and SARS outbreaks of the past two decades?
There are currently no vaccines to protect against any of the coronaviruses. But the research that was done during the previous epidemics may have shortened at least the exploratory and pre-clinical stages for the COVID-19 vaccine. That’s why we already have vaccine candidates in Phase I. The MERS-CoV vaccine is still under development, but the disease is primarily contained to the Arab peninsula. And since SARS-CoV disappeared, a vaccine is no longer necessary.
Are there ways to speed up the vaccine-development process through a coordinated effort between public and private entities?
The Coalition for Epidemic Preparedness Innovations (CEPI) is coordinating a majority of the efforts of vaccine discovery throughout the globe. They arrange funding, partnerships, and collaboration efforts between governments, pharmaceutical companies, and research organizations to speed up this process. For example, they brought together Moderna, the biotech company with a lead vaccine candidate in Phase I trials, and the National Institute of Allergy and Infectious Diseases (NIAID) to conduct the trial.
What are the most promising vaccine candidates right now?
Several companies are working on vaccine candidates. For vaccines, we have candidates from Moderna, Inovio, CanSino Biologics, and Shenzhen Genoimmune Medical Institute in the lead in Phase I trials. The others are in preclinical or exploratory stages. Interestingly, a trial is about to begin in Australia to test the effectiveness of the BCG vaccine against COVID-19. We know this vaccine is already safe, so that’s taken care of. It will be interesting to see if it is efficacious.
Do you see a coronavirus vaccination (once developed) becoming an annual occurrence, like influenza vaccinations?
It depends on how long the virus lasts and how fast it mutates. The SARS-CoV disappeared before a vaccine was ever developed. There are several hypotheses why this happened, but no one knows exactly why. The social distancing and isolation measures taken during that time probably played an important role in curbing the spread.
In terms of its mutation rate, influenza has lasted and has a very high mutation rate, so the virus changes rapidly, and several strains are often in circulation. So every year a vaccine is made after predictions are made of the strains that will likely be around that year. Even then, influenza vaccines don’t confer 100-percent protection, only because it is difficult to predict every single mutation.