How do the 3 new COVID-19 vaccines work?

Last updated: Apr 28, 2021
These shots are the first of their kind, and they’re true medical breakthroughs. Here’s a closer look at the science behind how they were developed.

The fight against COVID-19 has truly been a worldwide team effort. And because of that, the vaccines from Pfizer-BioNTech, Moderna, and Johnson & Johnson are the fastest ever developed.

“Years of research. Tremendous international collaboration. Innovative work by the National Institutes of Health and industry partners. And the inspiring willingness of [thousands of volunteers] combined to allow the delivery of these vaccines in less than a year,” says Helen Boucher, MD. She’s Chief of Infectious Diseases at Tufts Medical Center in Boston.

How were these shots created so quickly? How do they work? Are they safe and effective? Keep reading for the answers to these questions and more.

A new kind of vaccine

The COVID-19 shots developed by Moderna and Pfizer-BioNTech made headlines in December. They were the first to be authorized for emergency use by the U.S. Food and Drug Administration (FDA). But they broke ground for another reason. They’re also the first FDA-authorized vaccines to use mRNA technology. “[This] technology is new but not unknown,” Dr. Boucher says. “It has been studied for more than a decade.” But this is the first time they’ve been used widely in humans. 

The new shots work differently from typical ones. Many vaccines we get use inactive or weakened germs to trigger an immune response. That exposure to the virus or bacteria prepares the body to fight back if you catch the real thing later.

The mRNA vaccines, on the other hand, don’t contain any coronavirus at all. Instead, the shots only carry instructions (mRNA) for creating a part of it called a spike protein. Once you get the vaccine, your body begins to make the viral spike proteins from the mRNA instructions. 

These new spikes don't cause illness. But they do trick your body into building its defenses. The mRNA has a man-made coating that helps it get into cells. It never comes in contact with human DNA and breaks down within hours. Each of the mRNA vaccines requires two doses given three to four weeks apart.

The shot from Johnson & Johnson is called a viral vector vaccine. Instead of using a man-made coating to enter cells, this shot uses a harmless version of a different virus (the “vector”) to deliver the genes that make spike proteins. (In this case, it’s a modified cold virus.) The Johnson & Johnson shot contains short sections of DNA from the COVID-19 virus. They are the parts that code the instructions for making the spike proteins. They cannot make you sick.  

Once the DNA is delivered into cells, it makes mRNA and the rest of the process is like the mRNA vaccines. None of the genetic material gets into the nucleus of cells or ever comes in contact with human DNA. 

Four important notes to remember: 

  1. The cold virus used as a coating in this shot cannot make you sick. 
  2. Only part of the COVID-19 viral DNA is used. It cannot make you sick or change your DNA.
  3. Viral vector vaccines are more temperature stable. They don’t have the same refrigeration requirements as mRNA vaccines.
  4. You need only one dose.

All of the vaccines greatly reduce your risk for getting COVID-19. In the trials, they prevented 100% of hospitalizations for severe COVID-19 and deaths.  

As for those bits of mRNA and the viral vector that set things in motion? Your body destroys both and they vanish. All that’s left is the protection.

The long history of coronavirus research

While it might seem as if these new vaccines appeared out of nowhere, their foundation is deep. For years, labs around the world have been studying vaccines for other types of coronaviruses and other diseases. And mRNA vaccines for several illnesses have been in development for more than a decade. At least four of them have been tested in people.

Early publishing of the SARS-CoV-2 gene map (the name of the virus that causes COVID-19) helped, too. It allowed researchers to quickly find the bits of mRNA or DNA that made the spike proteins to use for the vaccines. 

The same is true for viral vector vaccines. Hundreds of studies have been published since the 1970s, according to the Centers for Disease Control and Prevention (CDC). Most recently, they’ve been used to fight Ebola, and they’re now being studied for HIV, Zika, and flu. 

All that hard work came together in the development of the COVID-19 vaccine, says Christine Turley, MD. She’s the Vice Chair of Research at Atrium Health Levine Children’s Hospital in Charlotte, North Carolina. Dr. Turley also leads STRIVE, a COVID-19 vaccine registry.

“Thirty years ago, we didn’t have the technology to do what researchers are doing now,” Dr. Turley says. “Sometimes people think scientists spend too much time working on things that don’t make a difference. But all that research is making COVID-19 vaccines possible.”

Investing in safety

So how did we get to this point so quickly? “We’ve shortened the timeline tremendously because of investments and advances in science,” says Robert H. Hopkins, MD, chair of the National Vaccine Advisory Committee. 

The U.S. government alone invested billions of dollars. Those efforts were supported by other government agencies, along with private and public institutions and companies worldwide.

“But we have not skipped any critical steps,” Dr. Hopkins says. “We’re doing large trials on human beings. At the same time, companies are building factories, bringing in the raw materials to make vaccines. We’re doing safety and efficacy studies. We’re also preparing to get vaccines out at the same time.”

Both the Pfizer-BioNTech and Moderna vaccines were studied in large trials with nearly 75,000 participants. The Johnson & Johnson trials included about another 40,000. All the studies had extensive outside oversight. 

“Data from [each] were publicly vetted by the FDA and further reviewed by the FDA advisory committee and the CDC,” says Dr. Boucher.

So far, the studies have shown the vaccines to be very safe when compared with the risk of getting COVID-19. Most people have only slight, short-lived side effects after receiving their shots. What’s important to remember if you have any of the common symptoms such as fever, arm soreness, or achiness: “They mean your immune system is responding,” Dr. Turley says. “It’s not a reason to avoid the vaccine. It means it’s working.”


The information in this story is accurate as of press time and posting. Getting vaccinated is one of the best ways to limit the spread of the coronavirus. It’s also important to continue practicing social distancing (keeping at least 6 feet away from people outside your household) and washing your hands frequently. You should also be appropriately masked any time you’ll be in public. According to the CDC’s latest guidance, this means layering a disposable mask underneath a snug-fitting cloth mask or placing a mask fitter over your cloth mask to ensure a tight fit. Because the situation surrounding COVID-19 continues to evolve, we encourage readers to follow the news and recommendations for their own communities by using the resources from the CDC, WHO, their local public health department, and our COVID member site

As of April 15, 2021, all Californians age 16 and older are eligible for a COVID-19 vaccine. Find out where to schedule an appointment.

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