How did we develop a safe COVID-19 vaccine so fast?

With the COVID-19 pandemic putting unprecedented measures on our healthcare systems and economies, unprecedented actions needed to be taken. That's why the U.S. Department of Health and Human Services started a program named "Operation Warp Speed" in an attempt to expedite the creation of a COVID-19 vaccine.

The crucial part of Operation Warp Speed was that it allocated funds for vaccine research and development. It also changed how pharmaceutical companies assess the risk of conducting large-scale clinical trials on a brand-new vaccine by the HHS guaranteeing the manufacturing of any successful vaccine candidates. The HHS also purchased allotments of the vaccines prior to knowing whether any of the Operation Warp Speed-funded companies would be successful.

The HHS deciding to substantially de-risk this process in order to expedite the creation of a COVID-19 vaccine proved to be a game changer for speeding up production, according to BioSpace. However, with rapid research development, some may be concerned that the vaccine was rushed, and with these concerns comes vaccine hesitancy.

So, how did scientists develop a safe COVID-19 vaccine so fast?

There was worldwide collaboration.

Amid a global pandemic, time was a luxury the world could not afford. Researchers quickly mobilized to share their coronavirus data with other scientists, according to Medical News Today.

There was ample funding made available.

Vaccine research is costly. In 2018, a study estimated the cost of early development and initial clinical safety trials for a typical vaccine to be in the range of $31-$68 million. Large scale trials would add to these figures.

For this reason, funding from the federal government was crucial to accelerate the timeline. In the U.S., Operation Warp Speed partnered with multiple institutions, including the National Institutes of Health and the Centers for Disease Control and Prevention, to develop, manufacture and distribute 300 million doses by early next year.

“I think the fact that the federal government offered huge incentives to companies to divert resources of their research and development teams to create a vaccine for COVID-19 had a lot to do with how quickly the vaccine was developed," said Dr. Norman Chapin, chief medical officer for McLaren Health Care’s Bay and Thumb Regions. "If there weren’t any assurances that there was going to be some financial benefit for these companies, I’m sure that would’ve impacted how quickly, or slowly, they invested resources into it. I mean, they’re businesses. I think the federal government had to really provide them with a guarantee that the cost of developing these vaccines would somewhat be offset.”

There was existing technology.

Both Pfizer and Moderna's vaccines use mRNA (messenger RNA) technology, which has existed for decades, but was too expensive to be used in a vaccination, according to Chapin. mRNA is also a very unstable compound, so trying to get it into a form that it can remain long enough in the body to be used to create the protein that it's encoded for, in this case the spike protein, had been a challenge, according to Chapin.

“If you look back in the literature, mRNA was first proposed nearly 30 years ago for oncology patients, and then some years later, they decided it could be an effective platform to develop immunity," Chapin said. "Treating cancer and preventing disease all deal with our immune system. So, they started to propose this concept that it could be used as a vaccination. I think for the last decade there’s been an increasing body of research that dealt with the problems they were encountering. In a way, the timing was good from the standpoint of having all those issues worked out, and then being able to take advantage of all the research to quickly create a strand of mRNA that, when read in a cell, would produce a spike protein to induce our immune response to that protein.

“It’s much safer than injecting a live virus, like we used to do and still do with some vaccines, or large particles of dead virus or dead bacteria," he continued. "mRNA degrades in the body within a couple of days and really can’t cause infection. So, people thought, from a safety standpoint, this technology would be better than the traditional approaches to induce immunity in the body.”

Traditionally, making vaccines required growing viruses or pieces of viruses — often in giant vats of cells or, like most flu shots, in chicken eggs — and then purifying them before next steps in brewing shots, according to the Associated Press.

The mRNA approach is radically different. An mRNA is basically a code of instructions for our body that we inject into our cells through the COVID-19 vaccine, according to Chapin. Researchers created an mRNA in the lab that tells the body to produce this spike protein to help the body create an immune response. It starts with a snippet of genetic code that carries instructions for making proteins.

“What we’re injecting isn’t part of the virus, but once it gets into the body it produces a part of the virus because it produces that spike protein," Chapin said. "That spike protein will exist in our body for a period of time, and then it will be destroyed. The immune response that is formed in the body will remain for some time.

“Every protein is what we call the 'expression of our genetic material,'" he continued. "The messenger RNA that comes from the nucleus into our cytoplasm is how that information gets transmitted for each unique person. It’s the messenger RNA that carries the message from our DNA, into our cell, into the factories in our cytoplasm to produce certain protein. So, mRNA is a naturally existing substance that our bodies use all the time. And, that’s why we call it messenger RNA because it carries the message from our nucleus into our cell.”

Additionally, mRNA cannot change a person's DNA, according to  Dr. Mark Hamed, Huron County Health Department medical director. 

“mRNA is a very safe, and very clean technology where you’re not actually putting a virus inside your body. You’re putting the instructions on how to fight a virus, which is really unique," Hamed said.

There were rigorous guidelines for clinical trials.

In the U.S., the FDA meticulously reviewed the data from each clinical trial phase before approval or, in the case of public health emergencies, before granting emergency use authorization.

Before any clinical trial can start, a data monitoring and safety board must approve a study protocol, Dr. Thomas Kenyon, chief health officer at Project HOPE and former director of the CDC Center for Global Health, told Medical News Today.

A phase 1 trial focuses on the safety of the vaccine candidate. Escalating doses of the vaccine are given to healthy volunteers to determine side effects and tolerability.

Phase 2 trials expand their recruitment and may include participants with health conditions such as obesity, cancer and diabetes. There is also active recruitment for participants of various demographics. The trial continues to test the safety of the vaccine and looks at the drug’s initial efficacy and how it affects the immune system.

Phase 3 trials recruit thousands of participants to measure the efficacy of the vaccine in preventing disease.

Given the worldwide safety concerns, two companies, Moderna and Pfizer — the latter of which did not take Operation Warp Speed funds but rather took funds from a similar German government program — decided to pursue this long-theorized but yet to be created vaccine technology: mRNA.

By mid-summer, Moderna and Pfizer had established themselves as the leaders in the race to develop a COVID-19 vaccine to be widely distributed. Before a vaccine is available to the public, it must go through several stages of testing. Both companies published initial Phase I/II clinical trial data last August and were pleased with the results.

Given these promising results, Phase III trials began with Moderna focusing its efforts within the U.S. and Pfizer taking a global approach. Between the two trials, more than 70,000 people were enrolled to receive either a placebo or a real vaccine and were subsequently sent out into the real world where their COVID-19 status was monitored for approximately 10 weeks, with the hope the results would be available before the year’s end, according to BioSpace.

In Pfizer’s Phase III trial, there were 170 total confirmed cases of COVID-19, with 162 of them occurring in the placebo arm. That’s an efficacy rate of approximately 95%. Furthermore, the company reported an extremely low number ( less than 2%) of adverse events, with none of them requiring immediate or critical medical attention.

Similarly, Moderna’s efficacy rate was approximately 95%, where the number of symptomatic COVID-19 cases in the treatment arm of the trial was only 11 compared to the 185 cases in the placebo arm. Perhaps even more impressively, while 30 of the 185 cases in the placebo arm developed into a severe case of COVID-19 requiring hospitalization, zero such cases were found in the vaccine arm.

"These vaccines are among some of the best we've ever made, when we had the first numbers — 95% of all symptomatic infections were prevented — 5% weren't protected," said Dr. Steven Lawrence, a Washington University infectious disease physician at Barnes-Jewish Hospital in St. Louis. "That's still phenomenal, compared to the flu vaccine which is 50-75% effective. That still means 1 in 20 people are still going to get infected, and breakthrough cases have always been known and will occur more often as a huge amount of virus is in the community, with more opportunity to get exposed and infected. That 5% will add up over time. The most important thing is to remember that the vast majority of people who have been vaccinated, even with breakthrough cases, the vast majority suffer only mild infections, vaccines provide extremely high protection against serious illness and severe disease, even against delta even eight months out, we still see those high levels of protection."

Both Pfizer and Moderna took those results to the U.S. Food and Drug Administration and their vaccines were granted emergency use authorization. Fast forward to Aug. 23, 2021 and Pfizer's vaccine won out. It was granted full approval by the FDA.

Pfizer developed and distributed a safe and effective vaccine for COVID-19 in less than a quarter of the time it took to achieve the same for mumps — the previous record holder.

Concerned about long term COVID vaccine side effects?

Doctors say you shouldn't be.

The Pfizer and Moderna phase III trials started on July 27, 2020, so researchers have been studying COVID-19 vaccine side effects for more than a year.

Serious side effects following vaccination are extremely rare. In contrast, you might deal with long-term health problems after getting sick with COVID-19.

“The effects of COVID-19 itself are much more serious than any kind of potential effects from the vaccine," Hamed said. "Now, do I think people will have side effects? Absolutely. It comes with the territory. But as far as those severe side effects, I think they’re very rare.”

Millions of people have received COVID-19 vaccines, and no long term side effects have been detected. Additionally, the COVID-19 vaccine is non-live. The vaccine does not contain any part of the virus. No non-live vaccine has ever been shown to cause side effects years later, according to the Chicago Department of Public Health.

“Do we have the evidence in front of us, of the million people that we vaccinated, that nothing bad happened to them 20 years later? No, we don’t know that," Chapin said. "We’re making some scientifically based assumptions on data we have from other vaccines. But again, the science would suggest that this is a safe vaccine, even in the long term, even though we don’t have data on this specific vaccine to prove that.”

The COVID-19 vaccine leaves your body within 72 hours. Your body makes antibodies triggered by the vaccine, and that is what sticks around to protect you. Hamed said you will not be able to see traces of spike proteins in people inoculated with the COVID-19 vaccine years later.