Dr. Kristen Marks, an associate professor of medicine in the Division of Infectious Diseases at Weill Cornell Medicine and associate attending physician at the medical center, leads the team conducting Moderna Therapeutics’s phase 3 COVID-19 vaccine trial at NewYork-Presbyterian/Weill Cornell Medical Center—one of dozens of medical centers around the U.S. where this still-experimental vaccine will be tested. Dr. Marks answered questions for the Weill Cornell Newsroom about Moderna’s vaccine and other vaccines designed to prevent infection by the coronavirus, SARS-CoV-2, that causes COVID-19.
What kinds of COVID-19 vaccine candidates are now in clinical trials?
All of the candidate vaccines aim at the same basic goal, which is to expose vaccine recipients’ immune systems to SARS-CoV-2 proteins, in particular the outer “spike” protein that the virus uses to attach and get into host cells to cause infection. The idea is that vaccine recipients’ immune systems will be prompted by this exposure to build up a reserve of immune cells— including those that make antibodies against the virus—so that the virus can be swiftly cleared from the body if it is ever encountered.
Some of these vaccine candidates are based on lab-made versions of SARS-CoV-2 proteins. There are other vaccines that use harmless viruses to make SARS-CoV-2 proteins in recipients’ own cells. The Moderna vaccine, which we’ll be testing in 500 volunteers at Weill Cornell Medicine, uses genetic material—called RNA—to enable the vaccine recipients’ cells to make SARS-CoV-2 proteins.
These different COVID-19 vaccine designs were developed and are now being tested all at once. We don’t yet know what strategy will work best for which people.
I want to emphasize that in these vaccine trials no one is being intentionally exposed to the SARS-CoV-2 virus—only to proteins from the virus, which on their own cannot cause infection.
Vaccines usually take at least several years to develop, yet some say a COVID-19 vaccine could be available within a year or so of the start of the pandemic. How is that possible?
In the United States, no safety steps are being skipped. COVID-19 vaccines are being tested with standard clinical trial designs, and their safety is being monitored very rigorously. But because of the urgency, different parts of the vaccine development process are now overlapping—for example, Moderna and other companies are already starting production of their vaccines so that they can have sufficient supplies if the vaccines are proven safe and effective.
What side effects should vaccine recipients expect?
The Moderna vaccine is a two-dose vaccine, with the second, booster injection given a month after the first injection. What the initial, phase 1 study of this vaccine showed is that the first shot generally brings minimal side effects, while the booster shot may be followed by flu-like symptoms for a couple of days—fever, headache, body aches—a bit stronger than those experienced by people receiving seasonal flu vaccines and similar to the shingles vaccine. Those symptoms are signs that the immune system is being activated by the vaccine.
How will this trial demonstrate if the Moderna vaccine is effective?
The plan is to enroll a total of 30,000 participants at all the medical centers involved in this clinical trial. Half will be randomly assigned to receive a placebo—a simple saline injection—and the other half the vaccine. Trial participants and the health care workers administering the study will not know who has received the vaccine and who has received the placebo, to avoid even unconscious bias in how we assess outcomes.
We will encourage trial participants to keep following the usual precautions such as wearing a mask and observing social distancing. But the statistical reality is that, over time in such a large group, some people will be infected with the coronavirus and will come down with symptomatic COVID-19 illness. If the vaccine provides protection, then there should be many fewer cases of COVID-19 among those who received it, compared to the placebo group.
The trial is designed to run for two years, but as soon as the trial managers see statistically clear evidence that the vaccine has provided protection without unacceptable side effects, they will go to the FDA to request approval for the vaccine. That could be as quickly as several months from now or it may take more time. If the FDA gives its approval, then the distribution of the vaccine will begin. People who participated in the study and received the placebo are not prohibited from taking any vaccine that gets approved.
What kinds of participants will you enroll in this trial?
We’re enrolling people who are at increased risk of contracting SARS-CoV-2 and/or who are at increased risk of getting sick with COVID-19 when they are infected. Here at Weill Cornell, we want at least a quarter of our participants to be over 65, because we know that older people are much more vulnerable to COVID-19. We’re also enrolling people who have medical conditions such as diabetes and hypertension that we know predispose them to COVID-19; people of color, who have been disproportionately affected by COVID-19; and front line workers who have relatively high risks of exposure to SARS-CoV-2.
What about children?
Children are not being enrolled in this clinical trial, simply because we’re focusing on the prevention of COVID-19 illness as an outcome measure—and children get sick with COVID-19 less often. Certainly, in the future a COVID-19 vaccine that is successful in adults will have to be tested in children to determine its safety, its optimal dose, and its effectiveness in preventing SARS-CoV-2 infection. Some vaccines studies are planned or underway in children as well.
What message do you have for prospective enrollees in your vaccine trial?
Although I think we’ll end up having a lot more people apply to participate than we have room for in this study, it’s also true that a lot of people view vaccines with a certain wariness. And I’m hoping that this trial and others can help educate people about the value and the safety of vaccines in general and particularly the value of a COVID-19 vaccine, which has the potential to help bring this global crisis to an end. Vaccine trial participants are really going to be heroes in this story in much the same way that frontline workers have been heroes.