Updated on January 19, 2020.
Two COVID-19 vaccines are available for emergency use in the United States and millions of Americans are either lining up or waiting for their turn to receive their shots.
Both are mRNA vaccines. One, known as mRNA-1273, was developed by Moderna. In clinical trials, the two-dose vaccine was shown to be 94.1 percent effective against COVID-19 and 100 percent effective against severe COVID-19. The other COVID-19 vaccine, known as BNT162b2, was developed by Pfizer and the German drugmaker, BioNTech. Pfizer said that its vaccine was 95 percent effective in clinical trials.
Both companies say that the efficacy of their vaccines is similar across age, race, ethnicity, and gender groups—although the vaccines haven’t yet been tested in children. Still, there are many people who are undecided about getting vaccinated or would prefer to wait and see how others react to the vaccine before they recieve it.
Income is one factor that may play a role in whether or not people decide to vaccinate, according to a recent Sharecare Community Well-Being Index (CWBI) Snapshot. Sharecare, in partnership with Boston University’s School of Public Health, examines the role that social well-being plays in overarching health. Social well-being is one of five interrelated elements of well-being in the CWBI, along with purpose, community, financial and physical well-being.
In a September 2020 nationally representative survey of 7,755 people, the CWBI Snapshot revealed an almost linear relationship between likelihood to get a COVID-19 vaccine and income. Those with higher incomes were more likely to indicate they will get a COVID-19 vaccine as soon as it's available to them than people with lower incomes.
The CWBI also found that smokers and people with asthma were more likely to report that they will immediately get a vaccine when it becomes available—even though they were less likely to wear a mask.
Overall, 49 percent of Americans said they will get the vaccine, with just 22 percent planning to be vaccinated right away, the CWBI survey found.
Why are so many people hesitating?
Skepticism about side effects. The most common side effects seemed to be short-lived and included pain, redness or swelling at the injection side, fatigue, muscle aches, joint aches, chills and headache. But there have been reports that side effects may be more intense than a sore arm commonly experienced after a flu shot.
Confusion about newer vaccine technology. Importantly, both front-runners are mRNA vaccines, a new type of vaccine that has never been approved for use in humans.
New types of vaccines or fast development tends to be a common source of vaccine hesitancy among people who usually accept vaccines, according to Bernice Hausman, PhD. Hausman is a professor and chair in the department of humanities at Penn State College of Medicine in Hershey, Pennsylvania. She has been studying the cultural contexts of vaccine controversy for decades.
The perception that research was rushed. “Naming the program Operation Warp Speed accentuates the idea that these vaccines were being developed very fast,” she says. “It doesn’t put a lot of emphasis on the safety protocols that are in place to make sure that the vaccines are safe for the population once they’re approved.”
Worries that political pressure played a role. At the same time, concerns about politicization of regulatory processes may have fostered mistrust. Hausman says that most people don’t distrust science per se, they question governmental scientists.
Responding to these concerns, researchers and government leaders have vowed transparency, that FDA approval isn’t handed out lightly, and that safety milestones must be met.
But how was it possible for these vaccines to be developed so fast? What safety checks did they have to pass to get to this stage?
Building on past experience
Surprisingly, luck may have played a role in the rapid development of a COVID-19 vaccine. As devastating as the pandemic has been, the coronavirus spike protein was an easy target. The spike protein is the “immunodominant” portion of the virus, meaning that it is the part that produces the strongest immune response.
The rapid timeline also benefited from years of research on vaccine development for other emerging infectious diseases. Organizations, such as the Coalition for Epidemic Preparedness Innovations (CEPI), the Bill & Melinda Gates Foundation, and the Wellcome Trust, had been laying the groundwork for years.
Research on vaccines for other coronaviruses that emerged over past decades, like SARS in 2003 and MERS in 2012, also prepared the way for tailoring a vaccine to the new coronavirus.
And even though mRNA vaccines have never been approved for humans, they are not entirely new.
Researchers drew on more than a decade of experience in developing mRNA vaccines for diseases like influenza, Zika, Ebola, and some cancers. In order to develop mRNA vaccines, scientists basically just needed to know the genetic code of COVID-19, which was faster than older approaches.
They also used artificial intelligence to do rapid-fire analyses that identified strategies most likely to work and most likely to ensure safety.
Eliminating red tape and streamlining development
Added to the scientific readiness, regulators used previous experiences with Ebola and HIV to expedite development. Frameworks used with these diseases were already in place for granting fast track status, accelerated approval, and EUA during a public health emergency.
Usually new drug development entails going through three phases:
- Phase 1: tests safety and efficacy in less than 100 generally healthy people
- Phase 2: adds dosage and the best way to give the vaccine as well as continued safety and efficacy testing in a larger, more diverse population of hundreds of people
- Phase 3: these are usually large, randomized, blinded and controlled trials, looking for rare side effects in tens of thousands of people.
Companies usually do these phases in sequence to see whether it’s worth paying for larger and larger trials. That can suck up time.
For COVID-19, that financial roadblock was taken away through large public-private partnerships, including Operation Warp Speed, which includes the Centers for Disease Control and Prevention, the FDA, the National Institutes of Health (NIH), the Biomedical Advanced Research and Development Authority (BARDA) and academia as well as pharmaceutical and biotech companies.
The outpouring of funding for a COVID vaccine enabled researchers to combine phases and step up development. It also improved collaboration and information sharing, further speeding things along.
Alongside trials, companies also started manufacturing vaccines, putting quality control mechanisms in place, and addressing barriers to distribution, knowing full well that some vaccines would be duds and their investment could be wasted. The idea was to make enough doses for the winners, and to have them ready for rollout once they were approved.
Multiple layers of guidance
Regulators were involved pretty much from the beginning. In April 2020, the NIH established Accelerating COVID-19 Therapeutic Interventions and Vaccines (ACTIV), to provide coordination across governmental organizations, industry, and non-profits, and to ensure clinical rigor and regulatory consistency.
On June 2020—before Phase 3 trials began—the FDA outlined standards for the development of safe, effective COVID-19 vaccines. The FDA required that companies should show, at minimum, that the COVID-19 vaccine prevents COVID-19 in 50 percent of people who receive it. By comparison, the seasonal flu vaccines prevent between 40 to 60 percent of flu illnesses.
Along with other best-practices requirements for safety, the FDA recommended that companies establish a pre-licensure safety data base that includes at least 3000 participants. The FDA also strongly encouraged including people who have been disproportionately affected by COVID-19, including racial and ethnic minorities, older adults, and people with underlying health conditions, such as diabetes, sickle cell disease, COPD, obesity, heart disease, asthma, cancer and HIV/AIDS, in clinical trials. Their guidance also included children, pregnant people and people of child-bearing age.
While any vaccine that receives FDA approval will eventually go through the full authorization process, the two front-runners are likely to be first rolled out using an EUA.
In October 2020, the FDA said that to receive an EUA, companies must submit at least two months of follow-up data. Because side effects associated with vaccination usually crop up within six weeks of vaccination, the two-month requirement was considered long enough to identify short-term adverse events related to the vaccine.
Reviewing the data on safety and effectiveness
As part of the trial process, companies are required to continually review safety and effectiveness. The review is conducted by a Data Safety and Monitoring Board (DSMB) made up of independent experts who are not employed by the company.
We saw those boards in action when AstraZeneca paused its vaccine trial after one participant developed neurologic symptoms. The trial was restarted after the DSMB decided it was safe to proceed, and after the FDA gave the green light in the United States.
When a company applies for FDA approval of a new vaccine, the FDA’s Vaccines and Related Biological Products Advisory Committee (VRBPAC) reviews clinical trial results and recommends whether or not to approve the vaccine. The VRBPAC is made up of a panel of outside experts who are not FDA staffers.
The CDC’s Advisory Committee on Immunization Practices (ACIP) also does their own review of trial results to decide whether a new vaccine is safe for use in the general public. ACIP is made up of 14 scientific and medical experts and one consumer advocate.
In the case of COVID-19 vaccines—including EUAs of the two front-runners—these committees still review the data, and the meetings are still open to the public. In addition, outside organizations have also said they will conduct their own review of the data.
In September the National Medical Association, the largest national organization representing African American physicians and patients, formed their own COVID-19 vaccine task force. And a number of states—New York, Connecticut, California, Nevada, Oregon, West Virginia, Washington, and the District of Columbia—are planning their own independent vaccine review panels.
Vaccine monitoring will be ongoing
As with any new drug approved by the FDA, rare, long-term side effects are not usually identified until the drug has been given to millions of people.
The FDA has existing systems to continue monitoring for efficacy and safety after a vaccine is approved. This can include requiring companies to conduct long-term safety and efficacy studies, called Phase 4 studies. The FDA also continues to inspect manufacturing facilities and test new batches of vaccines.
Several monitoring systems are also in place. These include the Vaccine Adverse Event Reporting System (VAERS), a voluntary reporting system run by the CDC and FDA, the FDA’s Sentinel Initiative, and the CDC’s Vaccine Safety Datalink (VSD).
The CDC also runs Rapid Cycle Analysis (RCA) which monitors safety data in real time and can alert health officials to problems as they happen so that the public can be notified quickly.
The CDC also plans to use an app called V-SAFE (smart phone enabled), which can be used to report and track side effects.
Vaccine rollout will take time
Even if the two front-runners receive EUA approval, most people are not going to receive them right away. Due to limited supply, rollout will be staged with highest risk individuals prioritized, such as front line health workers, nursing home residents and states having a role in distribution.
Hausman says that’s likely to boost vaccine confidence. By the time most people are offered a vaccine, more safety data will have accumulated. Fourteen COVID-19 vaccines are now in Phase 3 clinical trials, and choice may also increase in the months ahead.
The September CWBI survey found that more than half (27 percent) of the 49 percent of Americans who say they will get the vaccine, intend to wait a while rather than be among the first to line up. Meanwhile, 28 percent weren't sure what they will do, suggesting that more people may decide to get vaccinated over time as information becomes available.
At the same time, she stresses that it’s important to try to understand where people are coming from if they seem hesitant about these vaccines.
“It’s important that the issue of vaccination not be politicized,” she says. “We should be as empathetic as possible for the diversity of people’s views in our country around these questions.”
Hausman points out that she intends to get vaccinated.
“Because of my role in an institution of medical education, I would take the vaccine,” she says. “I would do so because I have watched ACIP deliberate carefully over months and I trust their collective judgment. I would also take the vaccine because I am tired of isolation and my elderly 96-year old father lives with me. I am trying to protect him.”
