How the COVID-19 Vaccines Were Made So Quickly—From the Lab to Clinical Trials to FDA Authorization
It took about a year for the vaccines to be developed, tested, and deemed safe and effective for the general public. Some people are skeptical of the shots because of their speed—here's why they shouldn't be.
On December 14, nine months after the pandemic forced the nation into quarantine, an intensive care nurse named Sandra Lindsay made history. Lindsay, the director of critical care nursing at Long Island Jewish Medical Center in New York, became the first person in the United States to receive a COVID-19 vaccine outside of a clinical trial.
Since that triumphant December day, almost 124 million people in the US—more than 37% of the total population—have received at least one dose of one of the three COVID-19 vaccines that have been granted emergency use authorization by the Food and Drug Administration (FDA). For many, the release of the vaccines seemed like the first step back to normal, pre-pandemic life, and they eagerly made an appointment for a shot as soon as they could.
Yet for many others, the vaccines are viewed suspiciously, thought to have been produced and tested too quickly to be safe. From conversations on social media to Zoom to real life, a sizable number of people across the nation are taking a wait-and-see attitude—or even a "no, never" stance regarding the shots. When the Associated Press conducted a poll in conjunction with the NORC Center for Public Affairs Research in February and asked 1,055 Americans why they would not get the vaccine, "I feel like they rushed it" was an answer that seemed to be echoed by others.
If getting the vaccine were only a matter of personal choice with no consequences, this high number of hesitant people would not be noteworthy. Yet according to medical experts, 70-90% of the population will need to be vaccinated to halt the spread of the virus. "The only path forward to actually getting our society back to normal is a vaccine," Ross Kedl, PhD, professor of immunology and microbiology at University of Colorado Anschutz School of Medicine, tells Health. "There has never been an infection against which we've achieved herd immunity without one." Not only can vaccines help reach herd immunity—aka, when enough people in a population have been vaccinated so that person-to-person transmission is unlikely—but they can prevent new, more dangerous variants from emerging.
For these reasons, addressing the concerns of those who do not trust the vaccine is a public health imperative. Here, medical experts detail why the vaccine's rapid development is not the result of bad medicine, but the payoff of bureaucratic efficiency and scientific know-how.
The first steps toward a COVID vaccine
By April 2020, just a month after COVID-19 was declared a global pandemic (and four months after the coronavirus first appeared in Wuhan, China), more than 90 vaccines were being developed by research teams across the world. That number rose to over 150 by July, highlighting how the scientific communities saw a vaccine as a critical component to stopping SARS-CoV2, the medical name of the virus behind the pandemic.
"The vaccine was looking at how to stop people from getting sick and dying—not [stop] an infection," Helene Gayle, MD a Chicago-based physician who co-chaired a committee for the National Academies of Sciences, Engineering, and Medicine that established a framework for equitable distribution of the vaccine, tells Health.
By March, the same month the US began shutting down businesses, workplaces, and schools in response to the pandemic, both Pfizer and Moderna had opened labs to find a vaccine. On May 15, their work was given a major boost when the Trump administration launched Operation Warp Speed. The program, a collaboration between the Pentagon and the Department of Health and Human Services, was intended to support pharmaceutical and biotechnology companies in everything from funding to expertise so a safe, effective vaccine could be available to the general public as quickly as possible.
Logistically, Operation Warp Speed assigned a team apiece (comprised of clinical trial specialists, epidemiologists, and budget experts) to each vaccine manufacturer. Weekly check-ins not only went through the particulars of the trials but also detailed plans for distribution and manufacturing.
By November, nearly $11 billion was awarded to seven companies for vaccine development. This included $2.5 billion to Moderna, which the company used to grow its workforce, upgrade its manufacturing space, and buy raw materials. In return, according to The New York Times, Moderna promised to deliver 100 million doses to the federal government. (Pfizer was one lab that declined funding, agreeing in July 2020 to sell 100 million doses of the vaccine to the US government for $1.95 billion.)
Operation Warp Speed was unarguably instrumental in accelerating vaccine production, in terms of providing funding and streamlining bureaucratic red tape. But there was another reason the labs were able to move at what might seem like breakneck speed. COVID-19 is a coronavirus, a group of RNA viruses that cause a range of respiratory, gastrointestinal, and neurological diseases—from the common cold to more serious illnesses like severe acute respiratory syndrome (SARS). Scientists have been studying coronaviruses and working on vaccines against them for many years. Because of this, scientists weren't exactly starting from scratch. "The vaccines were created by building on science developed over several decades," says Dr. Gayle.
The Johnson & Johnson vaccine was made via a method that has been safely used for some time in other vaccines. It relies on a disabled adenovirus, a type of virus similar to viruses that cause the common cold. "The adenovirus is essentially a replication-deficient virus shell that can be taken up into the cells in your arm but it cannot replicate," says Kedl. "It is basically a Trojan horse scenario: The SARS-CoV2 spike protein is hidden inside an adenovirus vector."
The vaccines by Moderna and Pfizer work differently. They are mRNA vaccines (or messenger RNA), which use a fragment of the virus's genetic material (or RNA) to teach the cells of a vaccinated person to make a protein that triggers an immune response. Antibodies are produced during the immune response that then offer protection if a person is infected.
Although mRNA vaccines are new, the research behind them is not. "The nature of the process by which you make these mRNA vaccines has actually been building for the last few years, such that you can rapidly produce them," says Kedl. "It's very easy to create a sequence that will match the virus. It's very easy to produce a vaccine that will represent the virus protein very, very well and very quickly."
How quickly? In the case of Moderna, two days. On January 11, researchers in China released the genetic sequence of the new virus. Researchers working with Moderna at the National Institute of Health used this sequence to find the gene for the virus's spike protein. They sent the data to Moderna via a Microsoft Word file. As the New York Times reported, scientists at Moderna took this information, plugged it into data they had created, and designed the mRNA vaccine on January 13. Less than one month later, on February 7, the first clinical batch was ready.
Once the vaccine is made, clinical trials begin
When a lab produces what it believes is a viable vaccine, the next step in the process is running a clinical trial and recruiting people for the trial. The first volunteer for the Moderna clinical trial for the COVID-19 vaccine got the jab in March 2020.
A clinical trial involving humans has three phases. In the first, a small number of volunteers are injected with the vaccine to test safety, gauge proper dosage, and identify side effects. The second phase expands the number of volunteers into the hundreds to further test safety. Many vaccines do not make it beyond this phase. Those that do go on to the third phase, which involves recruiting thousands of volunteers. Some are given the vaccine, and the remainder get a placebo. If at any point during these phases volunteers develop alarming reactions, researchers can pause or abandon the trial.
Kedl has spent his career studying the design and implementation of vaccine adjuvants (ingredients used in some vaccines to help create a stronger immune response). But last August, he was on the other side of science when he joined the third phase of the Moderna trial as a human volunteer. "It was clear from what I saw on the data before I signed up for it that this was going to be a very successful vaccine," he recalls. "It was a neat thing to be the guinea pig for once, get the immunizations and be able to contribute to something I felt was going to be meaningful."
He was not alone in his eagerness to test drive the vaccine. When the trials were ready to begin, participating academic institutions posted notices to find volunteers. And because of the urgency to create a COVID vaccine, national databases were also set up to find people. The response was enthusiastic, with tens of thousands signing on. "Many wanted to help find a solution to the pandemic," Daniel Kaul MD, a professor of internal medicine at University of Michigan, which participated in the trials, tells Health. "Others wanted an opportunity to get early access to protection from COVID-19."
The trials did not progress without a few hiccups. News reports emerged of adverse reactions in some participants during the first months. This led to a brief pause in the Oxford AstraZeneca vaccine trial in September after a phase 3 volunteer developed a severe, unexplained illness. (The AstraZeneca vaccine, approved in many European countries, has not been authorized for use in the US.) Johnson & Johnson also halted its trial for 11 days when one volunteer becoming sick, though it was never shown to be tied to the vaccine.
"These kinds of pauses are common," says Dr. Kaul. "Until the trial is completed we do not know if the vaccine is truly safe or if there will be uncommon but severe side effects in some people. That is part of the reason to do the trial, and that is part of the risk that participants take. We should all feel gratitude to study participants for that reason."
In addition, during both Moderna and Pfizer's trials, the companies were informed by Operation Warp Speed that they needed to have greater racial diversity in their participant pool. Because Black and Latinx communities had been devastated by COVID-19, it was of critical importance that the vaccine be proven safe for people of color. In response, each company recruited more Black and Latinx volunteers. Pfizer expanded the number of people in its trial its trial from 30,000 to 44,000, while the National Institutes of Health assisted Moderna in recruiting a more diverse group of volunteers.
While a number of people across the country continue to question the safety of the vaccines, the overwhelming belief of the medical community is that they are safe based on the results of the clinical trials. "The three COVID-19 vaccines currently authorized in the US were all rigorously tested in large clinical trials," Namandjé N. Bumpus, PhD, professor and director of the department of pharmacology and molecular sciences at Johns Hopkins University School of Medicine, tells Health. "Most of the side effects were mild to moderate and were in line with what would be expected from a vaccine." Adds Bumpus: "Each trial had a fully independent safety monitoring board and safety data have also been reviewed by the FDA and expert panels."
Though they may seem to have been conducted quickly, the trials were not expedited in a way that compromised safety. "You can't rush a vaccine trial because your immune system takes a certain amount of time to generate immunity, " says Kedl. "It takes a few months to produce all immunity. And then it takes time to assess that, and then more time to determine whether [the immunity] is efficacious or not. There's biology that you can never rush."
What you can rush is paperwork, manufacturing of the vaccine doses, and a number of bureaucratic steps that took place at the same time as the trials were underway. Normally they would wait until after completion, but the pandemic led to many things happening in tandem.
After clinical trials, the vaccine goes to the FDA
After a clinical trial has compiled data that prove effectiveness and safety, this research is presented to the FDA for approval to be used for the general public; it's the safety stamp given to everything from medication to food additives. In the case of the COVID-19 vaccines, however, the FDA didn't give the typical kind of approval. Instead, all three were granted emergency use authorization (EUA) from the FDA: Pfizer on December 11, 2020, Moderna on December 18, and Johnson & Johnson on February 27, 2021.
The FDA defines EUA as "a mechanism to facilitate the availability and use of medical countermeasures, including vaccines, during public health emergencies, such as the current COVID-19 pandemic." As Dr. Gayle explains, emergency approval is granted faster than traditional approval, which was necessary as deaths and severe illnesses rose. "Emergency use says you weigh the risks of the moment—the COVID crisis—against the minimal increase in knowledge you might gain by following the trials longer. It does not mean approval without normal safeguards in place," explains Dr. Gayle.
After receiving an EUA, it's expected that manufacturers will continue clinical trials to collect data that they can use when they apply for full FDA approval. Volunteers who participated in the trials (like Kedl) continue to be monitored to track their antibody levels and any related reactions. According to Reuters, Moderna and Pfizer will track all of its Phase 3 participants for two years to assess long-term protection and safety.
Where we’re at now with the vaccines
While millions of doses of COVID-19 vaccines are being distributed, vaccine trials are also underway (from Moderna, Pfizer, and Johnson & Johnson) to test the safety of the vaccine in babies, children, and pregnant women. As of March 2021, according to The New York Times Coronavirus Vaccine Tracker, 93 additional labs are conducting trials for the COVID-19 vaccine they've developed.
In addition, Moderna is working to create a booster shot that will be effective against the South African variant. Kedl predicts that such boosters may be necessary every few years, but he stresses that it is still too early to know with certainty. "All of this 'variant making' that the virus does takes time, so the slower the vaccines take to roll out, the better chance that new variants will have time to be generated," he says. "If the globe gets vaccinated quickly, then we have a chance at limiting new variants—and therefore the number and frequency of boosters needed in the future to protect ourselves against them."
These medical developments are happening against the backdrop of loosening restrictions when it comes to travel, work, school, and other public places. Fortunately, as more people get vaccinated—including those have been skeptical of the vaccines—herd immunity can be achieved, and day-to-day life really will become "normal" again.
The information in this story is accurate as of press time. However, as the situation surrounding COVID-19 continues to evolve, it's possible that some data have changed since publication. While Health is trying to keep our stories as up-to-date as possible, we also encourage readers to stay informed on news and recommendations for their own communities by using the CDC, WHO, and their local public health department as resources.
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