mRNA Vaccines: What Everyone Should Know

“[The data around the Covid vaccines was] probably some of the most convincing data for any vaccination program that we've ever had in human history…”

Jeff Coller, Professor of RNA Biology and Therapeutics, Johns Hopkins University

“The use of mRNA in vaccines has opened new doors beyond infectious diseases.”

Stephanie Pappas, freelance science writer

By most measures, the development of vaccines represents the greatest achievement of modern medicine. The World Health Organization estimates that global immunization efforts have saved roughly 154 million lives worldwide since 1974—about six lives every minute, every year, for fifty years. The recent addition of messenger RNA (mRNA) vaccines to our armamentarium began with the launching of the Moderna and Pfizer mRNA COVID-19 vaccines in 2021. These were the first mRNA vaccines approved for use in people and ushered in a new era in the field of vaccinology. In this week’s post, I provide a brief overview of how mRNA vaccines work, discuss the mRNA vaccines that are currently approved against COVID-19 and other infectious diseases, as well as the promising results of mRNA vaccines for certain types of cancer.

What is an mRNA vaccine? Vaccines help the body learn how to defend itself from disease without the dangers of a full-blown infection. (https://www.cdc.gov/vaccines/basics/explaining-how-vaccines-work.html). Traditional vaccines train the immune system by introducing a weakened, inactivated, or partial version of a pathogen directly into the body. They may also use a deactivated (“killed”) virus, a weakened (live-attenuated) virus, or isolated parts of the virus, such as a protein subunit. (https://my.cealandclinic.org/health/treatements/21898-mrna-vaccines). The immune system encounters these viral components (or the whole, disabled virus) and mounts a response—producing antibodies and memory cells—so that it can recognize and fight off the real pathogen later.

mRNA vaccines work differently; they teach your immune system how to recognize and fight a particular infectious agent without ever exposing you to it. They don’t use any parts of a virus, but instead, give the body instructions to make a recognizable part of the virus. The vaccine delivers mRNA instructions into some of your cells. Your cells temporarily make a harmless protein (or part of a protein) associated with the pathogen and display it on the cell’s surface. The immune system recognizes the protein and learns how to mount a response against it, so that if the person is later exposed to the actual virus, their immune system can respond quickly. (It is important to note that vaccine mRNA doesn't alter your DNA; it operates mainly in the cell's cytoplasm and does not need to enter the nucleus, where your DNA is stored.)

For example, COVID-19 mRNA vaccines instruct cells to make the SARS-CoV-2 spike protein. Your immune system recognizes that protein and develops antibodies and immune cells that recognize it. If you're later exposed to the actual pathogen, your immune system can recognize it more quickly and mount a stronger response.

Currently, the U.S. Food & Drug Administration (FDA) has only approved five mRNA vaccines for use in humans: three for COVID-19 (Moderna’s Spikevax and mNEXSPIKE, and Pfizer-BIoNTech’s Comirnaty), one for seasonal flu (Moderna’s mFLUSIVA), and one for respiratory syncytial virus, or RSV (Moderna’s mRESVIA). Behind these five, however, a much larger pipeline of mRNA vaccines—targeting other infections and, remarkably, certain cancers—is moving through clinical trials.   

COVID-19 mRNA vaccines. The COVID-19 mRNA vaccines developed by Pfizer-BioNTech and Moderna were the first mRNA vaccines authorized and approved for public use. They are widely considered a monumental scientific achievement. They were the first mRNA products to successfully pass large-scale Phase 3 clinical trials, receive emergency authorizations, and win full regulatory approval—all within a year’s time. Their development also spawned the 2023 Nobel Prize for Physiology or Medicine awarded to Katalin Kariko, a biochemist from Hungary, and Drew Weissman, a University of Pennsylvania immunologist and physician.

While traditional vaccines can take a decade or more to develop, the genetic sequence of SARS-CoV-2, the coronavirus that causes COVID-19, was translated into highly effective mRNA vaccines (showing over 90% protection in trials) in less than a year’s time. This extraordinary accomplishment was supported by the U.S. government’s “Operation Warp Speed,” a public-private partnership launched in May 2020 to rapidly develop, manufacture, and distribute COVID-19 vaccines. These vaccines are estimated to have averted 2.5 million deaths globally during 2020-2024 (sensitivity range estimates, 1.4-4.0 million) and save 15 million life-years (sensitivity range estimates, 7-24 million life-years). (Ioannidis, JPA, et al., “Global Estimates of Lives and Life-Years Saved by COVID-19 Vaccination During 2020-2024,” JAMA, July 25, 2025).

RNA viruses have the intrinsic capacity to mutate rapidly. To stay on top of new alterations of the SARS-CoV-2’s genome, it is therefore necessary to develop new versions of the COVID-19 mRNA vaccine periodically for use in vaccination programs—much like the annual flu shot. For the 2026-2027 respiratory virus season, the FDA approved updated versions of Spikevax, mNEXSPIKE, and Comirnaty aimed at the XFG variant, a descendant of the JN.1 lineage that has been circulating.

As older adults are at increased risk of severe COVID-19, it is recommended that people 65 and older, as well as younger people with one or more chronic conditions that put them at higher risk for severe disease, receive one of the two updated mRNA COVID-19 vaccines: Moderna’s mNEXSPIKE updated vaccine or Pfizer’s BioNTech’s updated vaccine. For those who prefer a protein-based vaccine, it’s suggested that the Novavax vaccine is a very good non-mRNA alternative.

Both Moderna and Pfizer have indicated that their vaccines would be available soon. (Astor, M, “F.D.A. Approves New COVID Vaccines, and They Should Be Available Soon,” New York Times, August 27, 2026). Sanofi, which distributes Novavax, said “doses would be available in the coming days with the timing varying by location.”

Moderna’s mFLUSIVA vaccine. Flu shots save thousands of lives every year in the U.S. and many more worldwide. In August 2026, the FDA approved Moderna’s mFLUSIVA, the first mRNA-based flu vaccine, for adults 50 and older. (mFLUSIVA received traditional approval for adults aged 50-64 years; accelerated approval was granted for those 65 and older, with a postmarketing effectiveness study planned for that population.)

In its Phase 3 trial—more than 40,000 participants across 11 countries—mFLUSIVA proved 26.6% more effective than a standard-dose vaccine at preventing confirmed influenza in adults ages 50 to 64, and its relative efficacy was 27.4% higher among adults age 65 and older. It is now being distributed for the 2026-2027 flu season. (Shenai, D, “Will the mRNA flu shot work better than a regular seasonal one? What the science says,” Nature, August 14, 2026).

Beyond its immediate clinical use, mFLUSIVA is notable as proof of concept for a manufacturing advantage inherent to the platform: because mRNA vaccines do not depend on egg or cell-based antigen propagation, strain selection can, in principle, occur closer to the start of a given respiratory virus season, potentially improving the match between vaccine and circulating strains.

Most important mRNA vaccines in development. Roughly half of known viral families use RNA rather than DNA as their genetic material, and scientists have identified several hundred distinct viral species—between 220 and 450— capable of causing human infection. Researchers in both academia and industry are now developing mRNA vaccines against some of the toughest remaining targets, including HIV, norovirus (a leading cause of acute gastroenteritis), and the DNA viruses Epstein-Barr virus and cytomegalovirus. mRESIVA, the RSV vaccine mentioned above, made history in 2024 as the first mRNA vaccine licensed for an indication other than COVID-19, targeting RSV in older adults—a pathogen historically responsible for substantial hospitalization burden in that population.

mRNA cancer vaccines. One of the most exciting recent mRNA vaccine developments deals not with an infectious disease but with cancer. On August 19, 2026, Moderna and Merck announced that their personalized mRNA vaccine, intismeran, combined with the cancer drug Keytruda reduced the recurrence/spread of high-risk melanomas compared with Keytruda alone. (Fieldhouse, R., Basu, M, “Moderna cancer vaccine stops melanoma returning: What’s next for personalized treatments?,” Nature, August 20, 2026). This came from a Phase 3 trial of 1,137 patients with high risk melanoma that had been surgically removed. It is the first time a personalized mRNA cancer vaccine has succeeded in a large, randomized trial. Each dose of intismeran is custom-built from a patient’s own tumor DNA, designed to help the immune system recognize and attack that specific cancer. The result builds on earlier trial data showing a 49% reduction in the risk of recurrence or death. Moderna and Merck are now studying the same individualized cancer treatment approach in lung, bladder, kidney, pancreatic, and stomach cancers.

mRNA vaccination trajectory in the U.S. On August 5, 2025, U.S. Secretary of Health and Human Services Robert F. Kennedy Jr. canceled 22 mRNA vaccine development projects and investments, pulling roughly $500 million in federal funding directed at the Biomedical Advanced Research Development Authority. (Jarvis, L, “RFK Jr.’s mRNA decision may be his worst yet,” Bloomberg News, August 7, 2025).  I am not sure whether the defunding and/or cancelling of mRNA vaccine development projects is the worst decision Mr. Kennedy has made that affects the public health of this country, but it is surely up there.

The move has drawn sharp criticism from medical and health experts. (Pappas, S, “Why mRNA Vaccines Are So Revolutionary—And What’s at Stake if We Lose Them,” Scientific American, August 6, 2025). As Jake Scott, an infectious diseases specialist and clinical associate professor of medicine at Stanford University said: “Scrapping the fastest platform we have is a reckless move rooted in a fundamental misunderstanding vaccinology.”

In under five years, mRNA vaccination has gone from an experimental idea to a licensed technology, covering three infectious diseases, with a proven cancer treatment now added to the list. The core ides—giving cells brief, temporary instructions to build a protein without ever touching your DNA—had adapted to new problems faster than any vaccine platform before it. Whether that trajectory continues at the same pace in the U.S. will depend as much on funding and regulatory policies in Washington as on the science itself. The science is here. Where is the funding?

funding for and scale back development of mRNA vaccine contracts