Moderna’s mRNA vaccine is the second COVID-19 vaccine to be authorized and fully approved for use in the U.S. Here, we give a rundown of basic facts about the vaccine and an overview of how it works.
Vaccine name: mRNA-1273, marketed as Spikevax
Design type: mRNA
Population: Adults and children 12 years of age and older
Dose number: Originally 2 doses, 28 days apart, with a third dose recommended for certain immunocompromised people and booster doses also available. But as of April 18, 2023, primary vaccination consists of a single dose of the omicron-updated bivalent vaccine. Older adults and immunocompromised people may get additional booster doses.
Efficacy: 93.2% efficacy in preventing symptomatic COVID-19 in adults two weeks or more after receipt of the second dose.
Safety: No serious safety concerns reported other than some rare allergic reactions and a rare association with heart inflammation. The shots, however, commonly elicit reactions in people that can include injection site pain, fatigue, headache, muscle or joint pain, and chills.
Doses administered: As of April 19, 2023, more than 232 million doses have been administered in the U.S. For the latest vaccination information, see the CDC COVID Data Tracker.
Expected timeline: First doses were administered beginning on Dec. 21, 2020 to prioritized populations, following the Food and Drug Administration’s emergency use authorization on Dec. 18.
Operation Warp Speed involvement: The U.S. government has devoted more than $4 billion to the development, testing and manufacturing of the vaccine, plus another more than $8 billion on purchasing contracts.
Storage considerations: -20°C (-4°F) for long-term storage; after thawing, vaccine vials should be stable at refrigerator temperatures for 30 days.
Just a week after the FDA authorized the first COVID-19 vaccine on an emergency use basis — Pfizer/BioNTech’s mRNA shot — the agency greenlighted a second, from the Cambridge, Massachusetts, biotech company Moderna.
Like its predecessor, the Moderna vaccine also uses an mRNA design, but it differs on the specifics, including the amount of time between doses, the amount of genetic material in each shot and the precise lipid nanoparticles that surround and protect the mRNA. That difference in fat formulation is thought to be why the Moderna vaccine doesn’t need to be kept as cold — a feature that should make it easier to distribute.
After releasing positive interim results from its phase 3 trial on Nov. 16, 2020, Moderna announced on Nov. 30 that its vaccine had an efficacy of 94.1% in preventing disease in adults. The company submitted its emergency use authorization, or EUA, application to the FDA the same day.
On Dec. 17, 2020, an external panel advising the FDA agreed the vaccine’s benefits outweighed the risks in a 20-to-0 vote, with one abstention, and the following day the agency authorized the vaccine for emergency use in people 18 years of age and older.
On Jan. 31, 2022, the FDA granted full approval to Moderna’s vaccine, for use in adults for the primary two-shot vaccination.
On June 17, 2022, the FDA authorized the adult vaccine for teens 12 through 17 years of age. Distinct pediatric versions of the vaccine, with a quarter and half as much mRNA, are also available under an EUA for children 6 months through 5 years of age and kids ages 6 through 11.
In August 2021, the FDA revised the EUA to allow for third doses of the vaccine in certain immunocompromised adults, given 28 days after the second dose.
The FDA previously authorized third dose “boosters,” which contain half as much mRNA as each of the first two shots, for non-immunocompromised adults at least six months after the second dose. After initially restricting third-dose “booster” eligibility to higher risk adults and people 65 years of age and older, the agency expanded booster access to all adults on Nov. 19, 2021. A CDC advisory committee concluded then that anyone 50 years of age and older or with risk factors “should” receive one, while adults below 50 without risk factors “may” receive one.
But with news of the fast-spreading omicron variant, the CDC began recommending boosters to all adults on Nov. 29, 2021. On Jan. 7, the FDA reduced the interval for receiving Moderna boosters, authorizing them for five months after the initial series instead of six.
On March 29, 2022, relying primarily on data from Israel, the FDA and CDC began allowing immunocompromised people and those over the age of 50 to receive a second mRNA booster four months or more after the previous dose. Citing a steady rise in cases and a “substantial increase in hospitalizations for older Americans,” the CDC said on May 19 that all people over the age of 50 and the immunocompromised “should” get a second booster.
On Aug. 31, 2022, the FDA authorized updated boosters that target the BA.4/5 omicron subvariants in addition to the original virus. These “bivalent” boosters replaced the earlier boosters and temporarily ended the era of counting vaccine doses, making people eligible for a single bivalent booster, two months or more after a previous vaccine dose.
On April 18, 2023, the FDA simplified the vaccination schedule further and ended the use of the original, monovalent mRNA vaccines. The CDC signed off on the changes the following day. Now, everyone age 6 and older is eligible to get one dose of the bivalent vaccine, with additional doses possible for older and immunocompromised people. For more on the updated vaccines, including what is currently authorized, see “Q&A on Omicron-Updated COVID-19 Boosters.”
While the United Kingdom was the first to authorize the Pfizer/BioNTech vaccine, the U.S. was the first country to permit the use of the Moderna vaccine, following substantial R&D and manufacturing support from the government and a collaboration with the National Institutes of Health.
What is in the vaccine and how does it work?
As with most other COVID-19 vaccine designs, the Moderna mRNA vaccine works by triggering an immune response against the SARS-CoV-2 virus’s spike protein, which sits on the surface of the virus and is what the virus uses to enter cells.
The vaccine is made of modified messenger RNA, or mRNA, wrapped in a special blend of fatty molecules known as lipid nanoparticles. The mRNA provides instructions for cells to make their own spike proteins, prompting the body to generate protective antibodies and activate other immune cells known as T cells. The lipids help deliver the RNA into cells and prevent it from being degraded too quickly.
Whereas the Pfizer/BioNTech vaccine includes 30 micrograms of mRNA in each dose, Moderna’s shot has 100 micrograms; the two vaccines also use a different mix of lipids. These differences may explain why Moderna’s vaccine appears to produce more expected side effects than its competitor.
As the Centers for Disease Control and Prevention has explained, there is no way to catch COVID-19 from this type of vaccine because the vaccine is not made of a virus. And because the mRNA from the vaccine doesn’t enter the nucleus — the part of the cell that houses DNA — it “does not affect or interact with a person’s DNA,” contrary to some online rumors.
How was the vaccine developed?
The Moderna vaccine was developed in collaboration with the National Institutes of Health. Researchers at the National Institute of Allergy and Infectious Diseases’ Vaccine Research Center were already working with scientists at Moderna on an investigational vaccine to protect against MERS, another disease caused by a coronavirus. As soon as the genetic sequence of SARS-CoV-2 became available in January 2020, the team was able to apply that knowledge to design a COVID-19 vaccine targeting the virus’s spike protein.
In mid-March 2020, the NIH began testing three different vaccine doses in a phase 1 trial involving 45 adults 55 years of age or younger. Two doses of the inoculation triggered the expected immune responses, including neutralizing antibody responses similar to those recovering from COVID-19, without raising any serious safety concerns. The trial was later expanded to include 40 older adults.
The company launched a phase 2 trial with 600 volunteers in May 2020 to confirm the dose and continue to assess safety.
Meanwhile, a preclinical study published in July 2020 showed vaccinated monkeys that were challenged with virus rapidly cleared the pathogen from their bodies. A study published the following month found that in mice, the vaccine successfully prevented infection in the lung and nose.
A phase 3 randomized controlled trial began in late July 2020 that included just over 30,000 volunteers across 99 sites in the U.S. Enrollment was slowed in September 2020 to increase minority participation. Because the trial only included people 18 years of age and older, Moderna began enrolling 3,000 teens as young as 12 in a combined phase 2/3 trial in mid-December 2020 and is also testing its vaccine in younger children.
How effective is the vaccine?
In the updated trial results reported to the FDA for full approval, the Moderna vaccine was 93.2% effective in preventing symptomatic disease at least two weeks after the second dose in people 18 years of age and older.
As we’ve explained before, that means that a vaccinated person has a 93% reduced risk of becoming sick, compared with a similar person who wasn’t immunized — although the true effectiveness of the vaccine outside of a trial may be lower, and the trial was conducted before the delta or omicron variants became widespread.
The efficacy figure is based on observing 744 symptomatic COVID-19 cases in the placebo group versus 55 in the vaccine group, out of around 14,000 participants in each group.
In late November 2020, Moderna reported that its vaccine was 94.1% effective in preventing COVID-19 disease. Those initial clinical trial results served as the basis of the FDA’s initial EUA for the vaccine in December 2020.
The vaccine also protects against severe cases of COVID-19. In the updated trial, 106 cases of severe COVID-19 occurred in the placebo group, compared with two in the vaccine group, for an efficacy of 98.2%.
The trials did not evaluate whether the vaccine prevents transmission of SARS-CoV-2, but other evidence suggests vaccination does reduce spread of the virus, although it cannot eliminate it.
It remains unknown how long vaccine protection lasts. For some people who are immunocompromised, data suggest that two doses may be insufficient and those individuals might benefit from an additional dose or two.
For people who are healthy, Moderna conducted an additional study to evaluate the safety and efficacy of a third “booster” dose of its vaccine. In September 2021, the company announced that giving a half-dose booster results in an increase in neutralizing antibodies, with similar side effects to the second dose.
The same month, the FDA authorized a booster dose, given at least six months after the initial two-dose series, for the elderly and other populations at increased risk. The FDA then expanded booster eligibility to all adults in mid-November 2021 and reduced the interval to five months in January.
Over time and against the highly contagious delta variant, the Moderna vaccine remained highly protective against serious illness in healthy people, although protection against infection or mild illness declined.
Against omicron, which was first recognized in southern Africa in November 2021, the vaccine is much worse at preventing infection and mild disease. It still provides relatively good protection against more serious illness, though, and boosters increase this protection.
A Centers for Disease Control and Prevention study found that during the omicron wave, adults who had received two doses of the Pfizer/BioNTech or Moderna vaccines had a 79% lower risk of dying or needing a ventilator if hospitalized with COVID-19, compared with unvaccinated adults. Those who had received a booster vaccine dose as well had a 94% lower risk.
On March 29, 2022, the FDA and CDC began permitting immunocompromised people and those over the age of 50 to get a second mRNA booster, four months or more after the last dose. The decision was based largely on data from Israel, which, while limited, suggested improved protection against severe COVID-19 for people 60 years and older after a fourth mRNA shot.
On Aug. 31, 2022, the FDA authorized omicron-updated boosters, including one from Moderna for people 18 years old and up, two months or more after a previous COVID-19 vaccination. For more, see “Q&A on Omicron-Updated COVID-19 Boosters.”
How safe is the vaccine?
No serious safety concerns were reported in the trials. As with the Pfizer/BioNTech vaccine, however, vaccine recipients have frequently experienced temporary side effects, including pain at the site of injection, swelling of the lymph nodes in the vaccinated arm, fatigue, headache, muscle or joint pain, and chills.
According to the FDA’s summary, these responses are more likely after the second dose and tend to be more severe in younger adults compared with those 65 years of age or older.
While scientists say this is a sign that the shots are working as they should, these reactions can be unpleasant.
Serious adverse events, which refer to potentially life-threatening or disabling events, occurred in 1% of participants in both the vaccine and placebo groups in the phase 3 trial. Only three such events were considered by the FDA to be likely due to the vaccine: one case of uncontrollable nausea and vomiting and two cases of facial swelling, both of which occurred in women who had had cosmetic dermal filler injections in the past six months.
At least a few serious allergic reactions — expected with any vaccine — have been reported with the Moderna vaccine. Data presented to the CDC advisory committee showed a rate of 4.9 cases of anaphylaxis per million doses of the Moderna vaccine, as of July 31, 2021, which is slightly higher than 1 to 2 per million instances that occur with other vaccines.
At this time, the only people the FDA says should not receive the Moderna vaccine are those who have had a serious allergic reaction to a previous dose of the vaccine or one of its ingredients.
The Moderna vaccine has also been linked to an increased risk of rare heart inflammation in young people. In late June 2021, the CDC’s Advisory Committee on Immunization Practices concluded there is a “likely association” between COVID-19 mRNA vaccination and myocarditis, or inflammation of the heart muscle, and pericarditis, or inflammation of the lining around the heart, in teens and young adults.
Based on data collected through August 2021, the highest reporting rate of either condition in the U.S. following vaccination with the Moderna vaccine was 56.3 cases per million doses, which was in 18- to 24-year-old males. That rate was slightly higher than the rate of 52.4 cases per million doses of the Pfizer/BioNTech vaccine.
Some data indicate that the Moderna vaccine is more likely than the Pfizer/BioNTech vaccine to cause rare cases of myocarditis or pericarditis.
Health officials have emphasized that the potential vaccine-related myocarditis and pericarditis cases are rare and the benefits of vaccination still outweigh the risks. Early evidence, the committee said, suggests these myocarditis cases are less severe than typical ones. The CDC has also noted that most patients who were treated “responded well to medicine and rest and felt better quickly.”
In its approval summary, the FDA said the reporting rates for myocarditis or pericarditis are higher in males under the age of 40 and are highest in males 18 through 24 years of age. “Although some reported cases [of vaccine-associated myocarditis/pericarditis] required intensive care support,” the FDA summary reads, “available data from short-term follow-up suggest that most individuals have had resolution of symptoms with conservative management.”
The agency also conducted its own benefit-risk assessment and concluded that even for the highest-risk males and with reduced vaccine efficacy against the omicron variant, the benefits of vaccination outweigh the risks.
The FDA is requiring Moderna to conduct additional studies to better understand the risk of the inflammatory heart conditions after vaccination. The CDC is also conducting its own survey to investigate potential long-term effects.
Editor’s Note: This story will be updated as necessary.
Editor’s note: SciCheck’s COVID-19/Vaccination Project is made possible by a grant from the Robert Wood Johnson Foundation. The foundation has no control over our editorial decisions, and the views expressed in our articles do not necessarily reflect the views of the foundation. The goal of the project is to increase exposure to accurate information about COVID-19 and vaccines, while decreasing the impact of misinformation.