mRNA flu shots: A new era for vaccinations?
Texas A&M Health experts break down the new immunization option and weigh benefits, efficacy and side effects
By LASHA MARKHAM for VITAL RECORD
BRYAN-COLLEGE STATION, Texas—As the 2026 flu season ramps up and millions of Americans prepare for their annual flu shot, they may encounter a new option: the first FDA-approved messenger RNA (mRNA)-based vaccine that gained approval for adults ages 50 through 64 and accelerated approval for adults 65 and older in August.
Until now, the flu shot lineup featured six vaccination options—using live viruses, inactivated viruses or viral antigens—delivered via needle injection or nasal spray. The mRNA vaccine has proven effective in a phase three trial and may open new possibilities for those looking to gain protection this season.
How do flu shots work?
Jeffrey Cirillo, PhD, Regents Professor and interim head of the Department of Microbial Pathogenesis and Immunology at the Texas A&M University Naresh K. Vashist College of Medicine at Texas A&M Health, said the different types of vaccines provide immunity in different ways.
There are two main types of flu vaccines: live and inactivated, he explained.
Traditional vaccines are cultured and produced over the course of several months once the flocks of geese and ducks from Canada begin their migration south, bringing that year’s strain of influenza with them, Cirillo said.
The live vaccine—currently only offered as a nasal spray—contains a version of the virus that has been altered to live in the cooler temperatures of your nose but not the warmer temperature inside your body. The virus replicates inside the nasal passages and triggers an immune response. By the time the virus has moved deep inside the body, it dies and protective immune cells have been generated.
The inactivated flu vaccine—which includes a version of the influenza virus that has been killed—doesn’t replicate but does introduce the body to the virus in a controlled way, teaching the body’s defenses how to recognize the virus and produce the right antibodies. There are four types of inactivated vaccines—standard, high-dose, adjuvanted and cell
“Both of the previous versions of the vaccine did have basically the whole virus. The live virus is live, so it replicates, whereas the killed one is just what it sounds like,” Cirillo said. “The problem with the inactivated virus and why it doesn’t induce as much of a response is that there’s no replication, so there’s no need to kill something off, and that part of the immune response is pretty important for responding to an actual infection.”
The third type of vaccine is called recombinant protein vaccine, said Moriya Tsuji, MD, PhD, professor at Texas A&M University School of Engineering Medicine.
This type of vaccine is fully synthetic and trains your immune system in a way that is similar to an inactive vaccine, Tsuji explained. It introduces the immune system to the virus without replication by providing your body synthetic proteins from the surface of the flu virus without using culturing like traditional vaccines.
All versions of the vaccine can produce side effects as the immune response develops, Cirillo said. Experiencing low grade-fever, minor body aches and some fatigue is normal and just means that the body is building defenses and responding to the virus like it should.
How does the mRNA vaccine work?
The mRNA vaccine—which is only available via needle injection—trains your immune system in a totally different way, without using live or inactivated virus.
The biggest benefit of mRNA vaccines is their production speed, Tsuji said.
Unlike the other versions of the flu shot, the mRNA vaccine does not require culturing, Tsuji said. The mRNA vaccine works by introducing flu virus messenger RNA into your body, providing the code to proteins on the outside of the virus. The mRNA vaccine—per its name—is providing a message to your immune system, instructing it on how it should respond when the time comes, he continued.
“If you inject messenger RNA, they translate into protein at the site of injection and they release proteins,” Tsuji said. “Then the proteins become immunogen and induce an immune response.”
Side effects from the mRNA vaccine are similar to those of traditional vaccines—low-grade fever, mild body aches and injection site pain. Even with trial data possibly indicating a slightly higher instance of these reactions, mRNA vaccine side effects and severity remain mild, overall.
Which vaccine should I get?
There are now seven different vaccines available on the market, with only some available to those 65 and older and to those with egg allergies.
Many vaccine options include a virus cultured in fertilized chicken eggs that is then extracted to produce a vaccine, disallowing that option for those with egg allergies, Tsuji said. Individuals with egg allergies can receive the recombinant protein vaccine, the cell cultured inactivated vaccine and, now—for those ages 50 to 64—the mRNA vaccine.
The high dose inactivated, adjuvanted inactivated or recombinant protein vaccine are recommended options for those over the age of 65, Tsuji explained.
For individuals over the age of 65 for whom egg-cultured vaccines are not an option, the mRNA vaccines add another choice with the recent accelerated FDA approval of the mRNA vaccine for those 65 and older—additional clinical trial pending.
In a recent clinical trial involving adults aged 50 and older, the mRNA flu vaccine provided approximately 27% greater protection against influenza than the standard-dose flu vaccine, Tsuji said. Although temporary side effects, such as soreness at the injection site, fatigue, and headaches, were more common with the mRNA vaccine, most were mild to moderate, and serious adverse events occurred at similar rates in both groups.
Tsuji said. The biggest downside to the mRNA, he continued, is that they might not provide protection for as long as the average flu vaccine—only about six months compared to the average nine months to a year for the traditional vaccines. Further studies are needed to determine whether they provide protection as long as traditional flu vaccines.
The nasal spray vaccine is a live vaccine available to healthy people ages 2 through 49, offering a needle-free option with few side effects.
Tsuji said he, personally, prefers to stick to traditional versions of flu vaccines while waiting for further research on the effectiveness and durability of mRNA-based vaccines. Meanwhile, Tsuji’s laboratory is developing a novel vaccine-enhancing ingredient, called an adjuvant, that has shown promising results in boosting mRNA vaccine effectiveness in animal studies, with the goal of advancing this approach to human clinical trials. For those looking to get vaccinated, Cirillo said he appreciates the promising new avenue for increased immunity the mRNA vaccine has shown to offer.
How important is getting a flu shot?
Immunizations are very important for preventing serious illness and mortality, Cirillo said. While they do not prevent you from getting the virus, they do prevent severe complications.
“The whole point is you don’t die from the virus,” Cirillo said. “The mortality rate, if you are vaccinated against the flu, is zero. It’s not like you’re not going to get sick or get infected with the flu. You can still get infected with the flu; it’s not necessarily going to prevent that. But what it does is prevent is you from having to go to the hospital or dying from the virus.”
The death rate nationwide for flu was about 0.4% in the 2024-25 flu season, he continued. The state of Texas documented around 2,000 deaths due to flu in the same time period—all in unvaccinated individuals.
Getting vaccinated against the flu is particularly important for those who are immunocompromised, elderly or very young, and those most vulnerable to complications, said both Tsuji and Cirillo. The flu shot is also important to protecting those around you, even if you may not personally have elevated risk of serious infection.
Experts agree that while we’re still learning about mRNA, the mRNA flu vaccine provides a solid and viable option for qualifying recipients to gain defense against the virus.
“With very little side effects and a really good response overall, you’re not going to really see any vaccine that’s better than this in terms of response,” Cirillo said. “It has a very good efficacy, very good safety. And that’s why the FDA approved it.”
###
ABOUT TEXAS A&M HEALTH
Texas A&M University Health Science Center (Texas A&M Health) comprises five colleges and schools (dentistry, medicine, nursing, pharmacy and public health), integrated University Health Services, several research centers and institutes, and numerous outpatient clinics with a shared mission of advancing health care for all. We serve the state and beyond with campuses and locations in Bryan-College Station, Dallas, Houston, Round Rock, Kingsville, Corpus Christi, McAllen and Navasota. Learn more at health.tamu.edu or follow @TAMUHealth on X (née Twitter).