Dr. Rachel Presti remembers the early days of the COVID-19 pandemic: struggling to get information, trying to figure out which treatments would be feasible and how to get them when the rest of the world needed them, too. Presti is a Washington University associate professor of medicine and medical director of its Infectious Diseases Clinical Research Unit. “I still remember feeling incredibly anxious,” she says. “When we heard that the government was funding this large-scale effort to create a network that would do Phase III vaccine trials, it was almost a relief. Yes, this is going to be a huge amount of work, but I can do something that could potentially get us out of this mess.”
In May, the U.S. Department of Health & Human Services announced Operation Warp Speed. The plan: fast-track the development, manufacture, and distribution of safe and effective COVID-19 vaccines with a goal of producing 300 million doses by January 2021. In June, the Trump administration selected five COVID-19 vaccines—those being developed by Moderna, Oxford University/AstraZeneca, Johnson & Johnson, Merck, and Pfizer—as frontrunners.
In July, Wash. U.’s School of Medicine and the Saint Louis University Center for Vaccine Development announced that they would be enrolling about 3,000 St. Louisans to participate in Phase III COVID-19 vaccine trials. Some of the participants will receive a vaccine; the others will get a placebo. SLU is taking part in the Moderna trial. As of press time, Presti’s team at Wash. U. had yet to announce its trial.
Subject for Change
SLU and Wash. U. expect to enroll more participants for COVID-19 vaccine trials after these initial studies. Visit slu.edu and wustl.edu for more information.
The work doesn’t end if the trials reveal a safe and effective vaccine. Researchers will follow participants for two years to rule out any delayed safety issues and to determine how long an immune response lasts. Dr. Daniel Hoft is the director of SLU’s Center for Vaccine Development and principal investigator for its Vaccine and Treatment Evaluation Unit, one of only 10 in the United States. He says that previous data from related coronaviruses suggests that a natural infection does not guarantee a long-term immune response. If the vaccine also does not induce a long-term immune response, researchers need to know. People might need to be vaccinated on a schedule, which would increase public health costs and add a layer of complexity.
The trials will also answer the question of whether the vaccine can stop people from getting COVID-19—and that’s why researchers are keen to enroll those who are likely to be exposed to the virus. They’ll track participants to see whether fewer people in the vaccine group get COVID-19 than in the placebo group.
But what about the risk? In his nearly 30 years of working with vaccines, Hoft has seen only a few that weren’t able to progress beyond Phase I because of an adverse event. “We’ve done probably 50 to 100 first-in-human vaccine trials,” he says. “It’s rare for Phase I to kill a vaccine because of a very common significant safety problem.”
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Coronavirus COVID-19 vaccine vial and injection syringe in scientist hands concept. Research for new novel corona virus vaccination immunization drug.
WHAT'S IN THE NAME?
The moniker Operation Warp Speed inspires hope that a viable vaccine will arrive soon, but it has left some wondering whether the research is being pushed through too quickly. (“Could they give it a nicer name?” Presti asks rhetorically, laughing a bit.) Vaccines typically take years or even decades to develop. There will be no cutting corners in this project, but it will move faster for these three reasons.
First, the funding is secured. Congress has set aside $10 billion for Operation Warp Speed.
The second reason is the sheer number of companies working on vaccines. According to The New York Times’ Coronavirus Vaccine Tracker, there are more than 165 vaccines in various stages of development worldwide. Thirty-two of those are in human trials. The more people working together, the faster the problem is likely to be solved.
Third, there’s the number of participants. For each of the five potential-vaccine trials, researchers are aiming to enroll 30,000 participants living in areas where there’s active transmission of COVID-19, not just in St. Louis. A participant pool this large will make it possible to see within six months a significant difference between the vaccinated and placebo groups. In the Moderna trial, a Data and Safety Monitoring Board will conduct interim analyses after 56, 106, and 151 confirmed cases of COVID-19 to see which participants received the vaccine. If the Moderna vaccine protects 60 percent of people who receive it, it can be considered effective.
COMMUNITY POOL
Altruism is inspiring hopeful trial participants, Presti observes. “What we’re hearing from a lot of people is ‘I want to do this for my grandparents’ or ‘I want to do this for my grandchildren,’” she says. “It’s empowering for a lot of people. It gives them something to do. Because otherwise what you’re supposed to do is stay home and wear a mask and stay apart from people.”
But the demographics of participation could present a challenge. For vaccines to work, they have to do so across ages and races—medications can produce different results, depending on recipients’ genetic makeups—but people of color have historically been underrepresented in clinical studies.
In 1993, Congress passed the Revitalization Act, which requires that all federally funded NIH clinical research prioritize the inclusion of women and people of color. However, since its passage, less than 2 percent of the more than 10,000 cancer clinical trials funded by the National Cancer Institute, part of the NIH, have included enough diverse participants.
Hoft identifies one major challenge: People of color who face health inequities also are often facing economic inequities.
Health insurance, a job that provides paid sick leave, and a car are all things that make it easier to participate in a clinical trial. “If it’s a decision between participating in an important vaccine trial and feeding your family…” Hoft trails off. “I don’t have any easy answers to that, but I know we need to focus on it, and we need to come up with solutions for the long term.” In the meantime, SLU is trying to aid participants who face these issues.
Further, some communities have “vaccine hesitancy” as a result of mistrust of health care systems and the government, which have, in some cases, misled and harmed them. At the same time, those same people are more likely to experience serious illness if infected with COVID-19 because of preexisting health issues.
Presti mentions the 1932 Tuskegee syphilis study, which examined infection in African-American men in Alabama over a period of 40 years. The men were misled about the purpose of the study and never given adequate treatment—even after 1947, when penicillin became the recommended treatment for syphilis. Locally, she points to the closing of Homer G. Phillips Hospital, in 1979. The hospital was built to serve the African-American community—both to treat patients and train medical professionals—in 1932, when St. Louis was still segregated.
SLU is working with the local Integrated Health Network and the St. Louis Metropolitan Pandemic Task Force to talk about the importance of the COVID-19 vaccine trials and facilitate recruitment, especially of people at higher risk.
As of press time, Wash. U. had not started enrolling people for the trials. However, Presti says, based on outreach the team was doing with public health departments, community groups, and individual physicians, trust-building and continued communication would be key to getting diverse participants. “It’s a continuous need to communicate, to treat people across the board with kindness and respect,” she says. Something as simple as pointing out the early adopters in the trial who do well can help.
“I think it can be hard, sometimes, from an academic setting,” she continues. “There are things that happened a long time ago, and sometimes you have all these young doctors who say, ‘You know, it was 50 years ago. Why are people so upset?’
“Yes, those things happened a long time ago,” Presti says, “but we haven’t made it right.”
MORE TO KNOW
FAST TRACK
OPERATION WARP SPEED’S STATS
THE PLAYERS
1. Department of Health and Human Services
2. Centers for Disease Control and Prevention
3. Food and Drug Administration
4. National Institutes of Health
5. Biomedical Advanced Research and Development Authority
THE GOAL
300 MILLION
doses of safe and effective vaccines, with the initial doses available by January 2021
THE CANDIDATES
1. Moderna (U.S.)
2. Oxford University/ AstraZeneca (United Kingdom)
3. Johnson & Johnson (U.S.)
4. Merck (U.S.)
5. Pfizer (U.S.)
FUNDING
$10 BILLION
from Congress
COST
UNKNOWN
But any vaccine funded by taxpayer dollars is free.
30,000
Number of participants in each Phase III vaccine trial
3,000
Number of St. Louisans
SOURCE: hhs.gov
