How the COVID-19 Vaccines Were Made So Quickly

On December 14, 2020, 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.

After that triumphant December day, over half the people in the US followed suit. By April 6, 2022, 81.9% of the population, 5 years or older, had received at least one dose of one of the three COVID-19 vaccines that had been granted emergency use authorization by the Food and Drug Administration (FDA) in December 2020. 69.8% of the population 5 years or older were fully vaccinated.

In August 2021, the Pfizer vaccine was fully approved by the FDA. The full approval for the Moderna vaccine followed in January 2022.

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 were 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 took a wait-and-see attitude—or even a "no, never" stance regarding the shots. About a month and a half after the emergency use authorization, January 28–February 1, 2021, the Associated Press conducted a poll in conjunction with the NORC Center for Public Affairs Research that 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.

Given that all FDA-approved or authorized COVID-19 vaccines are safe and effective, 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 more than 150 by July of that year, 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, told Health.

By March 2020, 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, which the Biden administration later restructured. The program, a collaboration between the Department of Defense 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 2020, 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 CNBC, 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. SARS-CoV-2 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," said 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," Ross Kedl, PhD, professor of immunology and microbiology at University of Colorado Anschutz School of Medicine, told Health. "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 (or messenger RNA) vaccines, 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 the Pfizer and Moderna COVID-19 vaccines were the first to use mRNA technology, the research behind them was not new at the time. "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," said 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, 2020, researchers in China released the genetic sequence of the new virus. Researchers working with Moderna at the National Institutes of Health (NIH) used this sequence to find the gene for the virus's spike protein. They sent the data to Moderna via a Microsoft Word file. Scientists at Moderna took this information, plugged it into data they had created, and designed the mRNA vaccine two days later, on January 13, 2020. 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 had spent his career studying the design and implementation of vaccine adjuvants (ingredients used in some vaccines to help create a stronger immune response). But in August 2020, he was on the other side of science when he joined the third phase of the Moderna trial as a 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," recalled Kedl. "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."

Kedl 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-19 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, told 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 2020 after a phase 3 volunteer developed a severe, unexplained illness. (The AstraZeneca vaccine, approved in many European countries, was not authorized for use in the US as of March 2022.) Johnson & Johnson also halted its trial for 11 days when one volunteer became sick, though it was never shown to be tied to the vaccine.

"These kinds of pauses are common," said 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's 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 them. In response, each company recruited more Black and Latinx volunteers. Pfizer expanded the number of people in its trial from 30,000 to 44,000, while the NIH assisted Moderna in recruiting a more diverse group of volunteers.

The overwhelming belief of the medical community is that the Pfizer, Moderna, and Johnson & Johnson vaccines are safe based on the results of the clinical trials. "The three COVID-19 vaccines 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, told Health. "Most of the side effects were mild to moderate and were in line with what would be expected from a vaccine." "Each trial had a fully independent safety monitoring board and safety data have also been reviewed by the FDA and expert panels," added Bumpus.

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," said 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 the vaccine producers could rush was 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 proved 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 right away. Instead, all three were granted emergency use authorization (EUA) from the FDA: Pfizer on December 11, 2020, Moderna on December 18, 2020, 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 explained, 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," explained Dr. Gayle.

After receiving an EUA, it's expected that manufacturers continue clinical trials to collect data that they can use when they apply for full FDA approval.

The Pfizer vaccine (marketed as Comirnaty) was fully approved on August 23, 2021, and Moderna (marketed as Spikevax) on January 31, 2022, but the trials continued. As novel variants such as Omicron or Delta emerged, vaccine boosters were developed. On March 29, 2022, the FDA authorized a second booster (or fourth overall dose) of the Pfizer vaccine for those 50 or older or certain immunocompromised individuals.

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.