‘Science is humbling’
said Offit, professor of pediatrics and director of the Vaccine Education Center at Children’s Hospital of Philadelphia.
It is not enough to know that a candidate vaccine produces an antibody response — even a vigorous response — in susceptible people or that hundreds of volunteers inoculated with it experienced no serious adverse effects. Not until a vaccine is tested in tens of thousands of people can doctors be reasonably certain it is safe and effective, and sometimes not even then.
Under normal circumstances, this process takes years. But these are not normal times, so the testing of potential COVID-19 vaccines is being collapsed into months, which could increase the risk of foulups. However, Dr. Francis Collins, director of the National Institutes of Health, gave his word that, despite being in a hurry to get an effective vaccine to the public, “we will not compromise on safety.”
Here’s how Offit, who is involved in supervising the COVID-19 vaccine trials, described the necessary sequence of events:
A prospective vaccine is first tested on laboratory animals that normally develop COVID-19 when infected with the virus, such as mice, to see if it prevents the disease. This is called “proof of concept” that the vaccine can work. It is followed by Phase I and Phase II trials in perhaps hundreds or thousands of human volunteers. Researchers look for evidence that the vaccine is safe and test different vaccine doses to find one that best results in antibodies that could protect against the virus. At least two vaccine candidates are already in this stage.
Now comes the big test, Phase III, a prospective placebo-controlled trial of tens of thousands of individuals to assess both safety and effectiveness. For one or more of the five promising COVID-19 vaccine candidates being fast-tracked, this stage is expected to start in July. Each Phase III trial will entail 20,000 people who get the experimental vaccine and a control (placebo) group of 10,000 unvaccinated people. The trials will take place in areas here and abroad that are already, or expected to be, “hot spots” for COVID-19 infections.
But depending on how prevalent the virus is this summer where the trials take place, it could take months — or even a year — to determine how well the vaccine prevents disease.
“That’s the only way to know if the immune response seen in earlier trials is protective in the real world,” Offit said. “If there’s little disease over the summer, it could be a problem. We may have to keep recruiting participants until enough people in the placebo group got sick to have a meaningful comparison with the vaccinated group. We can’t shortcircuit the process.”
He expects that the vaccine would have to be at least 70% effective to roll it out for mass use. But even then, he added, “we wouldn’t know for many more months how long immunity would last.” He cautioned against undue optimism about how good an approved vaccine will be. He said a vaccine might be considered acceptable if it prevents severe disease but not most or all infections that cause no symptoms or only mild illness.
“Science is humbling — it always comes up with surprises we can’t anticipate,” he said. “Once we have a vaccine, our job will be managing expectations.”
The first doses of an approved COVID vaccine will go to health care workers and residents and employees of long-term care facilities, then essential public servants as well as workers in food processing plants. Not until there are hundreds of millions of doses available — sometime in 2021 if all goes well — will the vaccine be offered to the general public.
Adequate protection against COVID-19 is expected to require two doses of vaccine. Thus, if the entire country were to be immunized, more than 600 million doses of vaccine would have to be manufactured.