How do mRNA vaccines work, and why are they safe and effective?

Messenger RNA, or m

RNA, vaccine technology burst onto the scene early in the COVID pandemic, leaving many people playing catch-up on the science behind the advance. Within the first six months of their availability, COVID vaccines prevented some eight million COVID infections, one study has shown. But despite the vaccines’ success, critics have fought against the COVID shots’ rollout and m

RNA vaccine technology more broadly. Recently, the Trump administration’s Food and Drug Administration initially declined to review an m

RNA vaccine for influenza. The FDA has since reversed its decision, but the Trump administration has made other moves to target the technology, including cutting nearly $500 million in grant funding for m

RNA vaccine projects. Despite setbacks, many scientists believe m

RNA vaccines will not only help control infectious disease but also improve cancer treatment. How do m

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All vaccines are designed to train the immune system to recognize a specific pathogen or other threat to the body. Vaccines that protect against infectious diseases have traditionally introduced a weakened or inactivated virus or bacterium or a distinctive protein from its surface to trigger an immune response that is milder than an infection. If the body encounters the same signal again, it is better prepared to fight off the invader.

In an m

RNA vaccine, the vaccine gives the body a section of m

RNA, genetic material copied from DNA that encodes one of the pathogen’s proteins. This piece of m

RNA acts as a template for the body to produce and then recognize that protein. Some vaccine skeptics have raised concerns about this use of foreign genetic material. Contrary to some claims, “it’s not going to change your DNA,” says Sabrina Assoumou, an infectious disease physician at Boston Medical Center and an associate professor at Boston University.

Extensive research has shown that the snippet of m

RNA enters cells but not the cell nucleus, where most of your genetic material is stored. And m

RNA is easily broken down by the body. Humans ingest m

RNA all the time from the food we eat, but our digestive system deactivates it. “Cells have safeguards so that we don’t get invaded by nucleic acids that just happen to be about,” says Jennifer Pancorbo, an expert in pharmaceutical biomanufacturing at North Carolina State University. To prevent the genetic material from disassembling too quickly, vaccine developers enclose the m

RNA in a specialized mix of tiny fatty molecules called lipid nanoparticles. These molecules form a protective bubble around the m

RNA that makes it easy for cells to absorb this genetic material. There the m

RNA remains for hours or, at most, a few days before a specialized enzyme breaks it down. Additionally, m

RNA vaccines include salts, sugars, acids and acid stabilizers, which make them more shelf-stable and enable them to be frozen. How do m

RNA vaccines compare with other types of vaccines? The oldest approach to vaccination in use today includes either inactivated pathogens—such as those in most modern polio vaccines—or pathogens that remain viable but have been weakened enough not to trigger disease—such as those in the measles, mumps and rubella, or MMR, vaccine. These “whole-virus” vaccines are simple to make, and researchers understand in detail how they operate in the body.

And they provide strong protection from an infection. The inactivated and weakened pathogens look “a lot like the bad guy,” Pancorbo says, “so it’s very easy for the immune response to be very specific and mount really quickly against that pathogen if you happen to be exposed to it.” That said, whole-virus vaccines can cause more unpleasant side effects, and in rare cases, weakened live pathogens can redevelop infectious capability.

Perhaps the most common vaccine approach is called a subunit vaccine, which contains only specific parts of a pathogen—often proteins. Subunit vaccines are safer than whole-virus ones because there’s absolutely no chance of a virus regaining the ability to infect people. But these vaccines sometimes require additional compounds called adjuvants or other strategies that have been shown to safely boost the immune system’s response to the vaccine.

Some examples of subunit vaccines include those that protect against respiratory syncytial virus (RSV), pneumococcal infections, whooping cough, hepatitis B, tetanus and human papillomavirus (HPV). The final broad category of vaccines in use today includes m

RNA vaccines. The vaccines in this category deliver genetic material that encodes a distinctive attribute of the pathogen. Instead of manufacturing a complete pathogen or pathogenic protein in a lab, your body’s own cells handle that step internally. What are the side effects and weaknesses of m

RNA vaccines? Like all vaccines, m

RNA vaccines can have side effects. As the COVID m

RNA vaccines rolled out, more than half of recipients reported reactions, known scientifically as reactogenicity, that included pain, fever and headaches. Although unpleasant, these side effects are short-lived and far less serious than an infection. And some evidence suggests having more side effects may be associated with a stronger immune response. The m

RNA COVID vaccines were also associated with a very rare side effect called myocarditis, or inflammation of heart tissue. This effect was more common among male teenagers and younger adults. Vaccine-related myocarditis occurs within a few days of getting the shot and affects about one in every 140,000 people who receive the first dose of a COVID vaccine.

COVID infection itself can also cause myocarditis, and the infection is associated with a much higher risk of severe heart issues than the vaccine. One further shortcoming of the m

RNA COVID vaccines is that they produce relatively short-lived protection against infection; specifically, production of immune cells called “memory” cells seems lower for them than it is for other types of vaccines, Pancorbo says. Scientists aren’t clear yet on why that aspect of the immune response seems flawed in m

RNA vaccines, given the strong initial response the products trigger, she says. What are the most exciting applications for m

RNA vaccines? By moving the manufacturing of the immune system’s target material into the body directly, m

RNA vaccine technology can speed up vaccine development—as it did with the COVID vaccines. That was crucial in the early days of the pandemic, as the virus that causes COVID, SARS-CoV-2, burned through a completely unprotected population. (Luck also contributed to the fast arrival of vaccines: researchers had already been working to design an m

RNA vaccine to protect against viruses similar to SARS-CoV-2.) As the virus has mutated, the m

RNA platform has allowed scientists to update COVID vaccines to better match the most prevalent strains. Researchers say the initial phases of a pandemic are perhaps the situation in which m

RNA vaccines are most valuable. The m

RNA technology is “a really great, flexible platform that helped us get out of the COVID-19 pandemic and will be useful in future outbreaks and epidemics and potentially prevent the next pandemic,” says Alyson Kelvin, a virologist and vaccinologist at the University of Calgary in Alberta. The same rapid development schedule makes m

RNA vaccines appealing for seasonal influenza vaccines.