Trials underway, but where do we go from here?
Experts describe the next steps in our race for a COVID-19 vaccine
With 125 vaccines in preclinical trials and a worldwide competition underway, hopes are running high for at least one workable vaccine to be ready for Americans by next year. In the Bay Area, major medical centers already have started recruiting volunteers.
That raises plenty of questions. This month, the National Press Foundation convened top experts to answer what we know so far.
Q Recruitment of volunteers has started, and they want 30,000 people each. That’s huge. Why do trials havetobesobig?
A “We need a cross section of the population that is ultimately going to be treated. … people who have a variety of medical comorbidities and a diverse population, including racial and ethnic minorities. We need to make sure that the vaccine is able to be effective in the entire population, not just the population typically volunteers for clinical trials.
“There’s also this need to make sure that we have a large enough safety database, so that we’re not surprised when we go into a really large population.”
Q Volunteers must donate blood. What are scien-
tists looking for? A Measurable signs that a person is immune — that is, protected against becoming infected and/or developing disease. These signs are called “correlates” of immunity — a phrase that we’ll be hearing a lot in the coming months.
There’s an understandable focus on antibodies, but they are just part of the story. Scientists are also looking at four types of T cells: T helper cells, which are responsible for cellular immunity and for helping the body produce antibodies; cytotoxic or “killer” T cells, which directly kill infected cells; other T cells, such as T-17 cells, which drive the inflammatory responses that help to control infections; and regulatory T cells, which help to contain the immune response, thereby preventing overreaction and damage to tissues.
“We need to get those immune correlates of protection. That will come from the first few vaccines. … It’s hoped that … we’ll understand the relationship between the efficacy we see clinically and the immune responses.”
• Dr. Peter Marks, director of the U.S. Food and Drug Administration’s Center for Biologics Evaluation and Research
Q Why does it take so long to get results?
A It takes time to recruit and vaccinate 30,000 people. If scientists are fast and lucky, that could be done by the end of August. Then they likely need to wait a month and vaccinate everyone again, with a “booster” shot. That puts us at the end of September.
Finally, they have to let nature take its course — that is, as people go out in the world, do they get infected? If volunteers are wearing masks and social distancing, that could take a long time.
“You’re not sending them all to that biker conference in Sturgis, South Dakota, and just telling them, ‘Good luck.’ You don’t want them to get sick. But on the other hand, the only way you’re going to know whether or not your vaccine works is if a critical number of people in your placebo group gets sick.”
• Dr. Paul A. Offit, chief of the division of infectious diseases at the Children’s Hospital of Philadelphia and co-inventor of the rotavirus vaccine
Q Why might we need a second dose?
A “Typically, when there’s a second or sometimes a third dose, you get this boost in the immune response… It’s the response that is most often associated with durability.
“So there could be protection with a first dose, but it’s likely to be more so and longer lasting with the second dose. I think the durability is going to be very, very important with our COVID-19 vaccines.” • Dr. Leonard Friedland, director of Scientific Affairs and Public Health, Vaccines, GSK
Q If a vaccine doesn’t actually prevent disease but just reduces its
severity, that’s still helpful, right? A Perhaps. But it could inadvertently boost the risk of transmission.
“If you have a vaccine that essentially just creates more asymptomatic carriers, we’d have to look very closely about whether that is a safe vaccine to deploy.”
• Dr. Peter Marks, director of the U.S. Food and Drug Administration’s Center for Biologics Evaluation and Research Q Is there worry about side effects? When would we start seeing those? A “What the FDA typically requires is that with a new vaccine and investigational vaccine that’s never been licensed in that class, people are followed for at least six months if not for a year.
That’s just not feasible or practical, given the public health crisis right now, but I would say at least a month would be important.”
• Dr. Leonard Friedland, director of Scientific Affairs and Public Health, Vaccines, GSK Q When do you decide whether it’s safe enough and ready for approval? A Clinical studies have “end points,” which are statistically significant measures of effectiveness. Vaccine makers will conduct an interim analysis of their data, then present it to the National Institute of Health’s Data Safety Monitoring Board. Normally, it takes several
months before a trial’s data is formatted and given over to FDA in a license application.
“In this case, what we want to do is shorten that time very significantly, potentially, by not requiring the same formatting into the application for a license application … We are using expedited review times for submissions.
We would want to see the end points and all of the data that we would normally want to see as part of the primary analyses, but we wouldn’t stand on ceremony … To wait several months potentially for that formatting to occur while people continue to get COVID-19, that’s a real concern for us.”
• Dr. Peter Marks, director of the U.S. Food and Drug Administration’s Center for Biologics Evaluation and Research
Q Then would you approve it?
A There likely won’t be enough understanding of a vaccine to allow formal approval. But because of the public health emergency, FDA would consider an Emergency Use Authorization, which allows the distribution of an unapproved vaccine to the public.
“It is possible that we could issue an emergency use authorization, once studies have demonstrated the safety and effectiveness of the vaccine.” • Dr. Peter Marks, director of the U.S. Food and Drug Administration’s Center for Biologics Evaluation and Research