What we know about the safety, efficacy of mRNA vaccines amid recent scrutiny

Over the last several days, the safety and efficacy of messenger RNA, or mRNA, vaccines have come under intense scrutiny.

On Tuesday, the U.S. Food and Drug Administration announced plans to limit access to future COVID-19 shots -- two of which are mRNA vaccines -- to those aged 65 and older or with high-risk conditions. The agency will require further scientific trials to greenlight the shots for younger age groups.

The agency also sent letters to both Moderna and Pfizer last month telling them to expand the warning labels on their mRNA COVID-19 vaccines to broaden the people who may be impacted by the risk of heart inflammation as a possible side effect.

Infectious disease experts told ABC News that mRNA and mRNA vaccines have been studied for decades, the vaccines are safe and effective, and that the shots were instrumental in saving lives during the COVID-19 pandemic.

“Here’s the bottom line: mRNA vaccines for COVID, according to estimates from Yale School of Public Health, saved 3.2 million lives,” Dr. Peter Hotez, a professor of pediatrics and molecular virology at Baylor College of Medicine in Houston, told ABC News.

“So instead of 1.2 million Americans who lost their life because of COVID, it would have been a 4.4 million,” he added. “So, I think it's unfortunate that anti-vaccine activists target mRNA vaccines like they do, but it is a good technology.”

What is mRNA?

mRNA was discovered independently by two teams in 1961 including French and American molecular biologists.

Dr. Peter Chin-Hong, a professor of medicine and infectious disease specialist at the University of California, San Francisco, said breakthroughs in developing mRNA vaccines began in the early 2000s, eventually leading to the development of COVID-19 vaccines in 2020.

While most vaccines use a weakened or inactivated virus to stimulate an immune response, mRNA vaccines teach the body how to make proteins that can trigger an immune response and fight off an infection.

“The way that it works is that it doesn't even go into the nucleus [of the cell]. It enters the outside of the cytoplasm, or the watery substance outside of the nucleus, and basically instructs the cell to make proteins,” Chin-Hong told ABC News. “But most importantly, it self-destructs in matter, at the most days, and it dies.”

He continued, “So mRNA goes away, but the products which are the most important thing -- the proteins and antibodies -- remain, and that's why we get protection.”

Chin-Hong also addressed another piece of misinformation that has circulated, implying that mRNA vaccines could alter DNA in the nucleus.

“Our cells can't convert mRNA to DNA because the mRNA doesn't enter the DNA, which is in the nucleus,” he added.

How do we know it’s safe?

Chin-Hong said that during the large-scale clinical trials for COVID-19 mRNA vaccines, in 2020, more than 70,000 people were involved in the Pfizer-BioNTech and Moderna trials combined.

Additionally, 37,000 people were involved in Moderna’s clinical trials for its RSV vaccine, Chin-Hong said.

Researchers found that side effects -- including fever, arm pain and swelling at the injection site -- for the COVID-19 mRNA vaccine were like those of traditional, non-RNA vaccines and they had short-term efficacy rates of more than 90%.

Additional studies have found that booster safety was consistent with safety reported for primary vaccination.

“There are all these databases that are used to follow reports of people, not only in this country, their experience using vaccines, but also in other countries, many other countries as well,” Chin-Hing said. “There have been multiple studies since 2020 showing there's no impact in fertility, stroke, all the things that people have worried about.”

Hotez said no vaccine technology is perfect, including mRNA technology, but it has its advantages such as being able to be designed more quickly traditional vaccines, allowing them to be deployed quicker.

He disagrees with the FDA decision to limit future COVID-19 vaccine shots because COVID has long-term consequences such as long COVID and delayed cardiovascular disease.

“I think there are many younger adults, or those under the age of 65, who are concerned enough about long COVID or downstream heart disease to want to have to be able to get the mRNA vaccine,” he said.

What about myocarditis?

Questions have swirled around how myocarditis, which is inflammation of the heart muscle, occurs after COVID-19 vaccination.

Myocarditis can cause arrhythmias, which are rapid or abnormal heartbeats. It can also cause the heart muscle to weaken, resulting in cardiomyopathy, which affects the heart's ability to pump blood effectively.

Cases of myocarditis and pericarditis -- inflammation of the sac that contains the heart -- have been observed rarely after COVID vaccination, according to the Centers for Disease Control and Prevention.

When they have rarely occurred, it has been among young adult males, typically between ages 18 and 29, within seven days after receiving the second dose of an mRNA COVID vaccine, the agency says.

The FDA, in asking the vaccine companies to expand their warning labels, cited “new safety information” -- data from one of the agency’s safety surveillance systems and a study published in October that followed people who developed myocarditis linked to COVID vaccines.

Chin-Hong said the risk of myocarditis is much higher after COVID-19 compared to after vaccination, and that contracting COVID itself is higher.

“The risk of COVID is much higher in general. If you look at it, 22 to 31 cases per million [among] 18 to 29 years old as an example,” he said. “At the time when these vaccines are used very often in that group, [myocarditis risk] is 1,500 per million. So, you're talking about 22 to 31 per million versus 1,500 per million.”

ABC News' Youri Benadjaoud contributed to this report.