In December 2020, mRNA vaccines leapt into the limelight as a response to the COVID-19 pandemic. To date, millions of people have received at least one mRNA vaccine, and researchers estimate that the shots have prevented more than two million deaths in the US alone.
Although this may have been the first time many people heard about mRNA used as a vaccine platform, it was hardly a new idea. The history of nucleic acid vaccines extends back to the end of the 1980s and the early 1990s, with many groups exploring the immunostimulatory effects of RNA and DNA.
In the 1990s, Deborah Fuller, today an immunologist at the University of Washington, was working at Agracetus (today PowderJect Vaccines Inc), a biotech company that was initially exploring genetic engineering in crops. Fuller and her team delivered genes by injecting them directly into plant cells, and some became interested in using DNA as a gene therapy. They started studying this concept in animal models, but after seeing antibody responses, the scientists switched to vaccine research, focusing on HIV. Fuller and her team showed that DNA vaccines delivered directly into cells produced T cells specific to the targeted HIV antigen.
Several other researchers found their way to DNA vaccines around this time as well. “It was an exciting [time] knowing we were pioneering an entirely new concept in vaccination,” Fuller said. Despite early successes in animal models, though, when DNA vaccines went into the first human clinical trials, “They were abysmal,” Fuller recalled.
While many researchers left the DNA vaccine field, Fuller remained, expanding into RNA vaccines as well. After COVID-19, several researchers jumped into studying mRNA’s potential for vaccines and therapeutics. It looked like mRNA had finally broken nucleic acid vaccines into the mainstream.
However, in August 2025, the US Department of Health and Human Services (HHS) canceled $500 million in funding related to mRNA vaccine research under the Biomedical Advanced Research and Development Authority (BARDA). Some contracts, like a late-stage investigation on an influenza vaccine from the biotechnology company Arcturus Therapeutics, were allowed to continue. Others, like mRNA vaccine studies exploring a Marburg vaccine from Moderna, were canceled. Nonetheless, the action sent a shockwave through the mRNA vaccine research community. Later, in February 2026, the FDA initially declined to review an application for an mRNA-based influenza vaccine, disagreeing with the use of control groups in the study. The agency reversed its decision two weeks later.
In response to these events, some researchers are concerned about the future of mRNA technology research and how the US’s disinvestment in it will impact public health. Others, including Fuller, believe that the promise of mRNA vaccines and therapeutics won’t come to a grinding halt anytime soon, but the change in the US’s support for the technology could shift where the next big breakthrough happens.
mRNA Technology Transformed Vaccine Development Timelines
Years before the COVID-19 pandemic, researchers had realized mRNA’s potential as a platform for rapidly developing vaccines against emerging infections.5 In fact, prophylactic and therapeutic mRNA vaccines were already in clinical trials.6-10
One of the advantages of mRNA vaccines is how quickly they can be produced. Unlike subunit or inactivated vaccines, the vaccine agent does not need to be grown, expressed, or purified from another system. The synthesis for mRNA vaccines is standardized, so once researchers have the sequence, they can immediately begin producing vaccines.
This saves valuable time—the world saw during the COVID-19 pandemic how quickly the mRNA vaccines were produced. “For pandemic response certainly mRNA technology is the most advanced or the best approach to date,” said Andrea Carfi, a vaccinologist and chief scientific officer at Moderna. Moderna is exploring mRNA-based vaccines against other pathogens that are known outbreak risks, such as Zika and Marburg virus.
But this expedited production timeline is also advantageous for seasonal vaccines. Currently, to make an influenza vaccine, scientists in the US identify the circulating strains in the spring before the year’s flu season—meaning the shots are designed a full six months before their administration. For rapidly mutating viruses like influenza, this can lead to mismatches between the vaccine strain and the currently circulating versions of the virus, decreasing the shot’s efficacy. In contrast, mRNA vaccines can be designed closer to the flu season, lowering the chances of mismatches.
I’m very excited about things that we’re already doing, but I’m also excited where the technology is going
—Andrea Carfi, chief scientific officer at moderna
This speed also makes it much easier for researchers to test different vaccine antigens. Researchers can quickly produce multiple mRNA sequences to trial and determine which ones lead to protective immune responses. Carfi added that mRNA technology also makes it much easier to combine multiple antigens into one vaccine, which is especially helpful against complex pathogens, like bacteria, or those with multiple strains, like norovirus.
Another advantage to mRNA vaccines is safety; patients don’t need to be exposed to an inactivated pathogen. “The mRNA technology allows us to really define and design the antigen and the part of the virus or the pathogen that we want to present to the immune system in a detailed way,” Carfi said.
Finally, because mRNA vaccines deliver the nucleic acid to the cell, which then produces it internally, this platform induces cellular immunity, like T cells, very efficiently in addition to antibody responses. This improves protection against a pathogen, including in infections where cellular immunity is key to defending against that agent. The ability to engage this arm of the immune system has helped researchers like Fuller explore how the immune system responds to difficult pathogens like HIV. Understanding this T cell engagement may pave the way for protective or therapeutic vaccines against this infection. Additionally, Moderna is exploring mRNA vaccines against Epstein-Barr virus and herpes virus, as both pathogens latently infect cells and require cellular immune responses to protect against them.
The ability to target latent pathogens caught the attention of Ulrike Protzer, a virologist at the German Center for Infection research (DZIF). In partnership with the German biotechnology company Ethris, Protzer and her team at DZIF are exploring how to use mRNA as a therapeutic vaccine platform to deliver cytokines and antibodies to the liver to induce antiviral immune responses in that area. “That’s also a nice way to not having to produce them recombinantly and inject them but produce them directly in the body with the right modifications and everything you want,” she said.
Recent Decisions Strain the mRNA Vaccine Revolution
While mRNA appears to be maintaining the fame that the pandemic thrust upon it, the technology and the researchers studying it recently experienced some obstacles.
Even before HHS canceled funding for grants using mRNA in August, the agency diverted money originally set aside for updating COVID-19 vaccines to development of a universal flu vaccine that, instead of mRNA, used inactivated whole virus strains. “It’s an old technology, and it’s not likely to work. There’s a reason why we pivoted away from these older technologies into something newer and why mRNA was so promising,” said Gigi Gronvall, a health security scholar at Johns Hopkins Bloomberg School of Public Health. She added that pivoting away from mRNA vaccine technology was a major setback for US public health.
Fuller agreed. “Other approaches may go forward, but are they going to be the best approach? [The way] I see it, you should support all of the potential promising approaches, and may the best vaccine strategy work,” she said.
Earlier this year, mRNA vaccine developers and researchers alike also raised their eyebrows at the FDA’s announcement that it would not review an application for an mRNA-based flu vaccine from Moderna. The agency released a statement that this was over a disagreement about the control group that the company used. Moderna petitioned this, citing that the strategy was previously approved by the agency, and the FDA reversed their decision. The agency has committed to making an approval decision by August 5, 2026.
Share this article
Carfi added that, for vaccine research specifically, there has been an increase in the general distrust of vaccines from the public.11In fact, Jayantha Bhattacharya, the director of the National Institutes of Health, said on a podcast that the reason why HHS cancelled contracts for projects involves mRNA vaccines was because the public did not trust them. While Gronvall was not convinced that this rationale was the full reason for the decision, she added “It’s [Bhattacharya’s] job to actually produce trust in the technology that is the best [and] that will actually help people the most in an emergency.”
Instead, she said that these leaders moved away from mRNA technology for political reasons, which will leave the US far more susceptible to and less prepared for future pandemics.
The apparent distaste for mRNA vaccines at the FDA and at HHS more broadly could deter companies from trying to bring these products to the market, Gronvall worries. “What has been really frustrating watching this process is that companies rely on predictability,” said Gronvall, who has previously worked on recommendations to make FDA approval pathways more streamlined. She added that agencies changing expectations and processes during application reviews for vaccines introduces uncertainties that can deter companies from investing resources into developing mRNA vaccine technology.
This stance may also create international ripple effects. Protzer noted that she has seen skepticism among some pharmaceutical investors about if mRNA vaccines will be a good investment for non-emergency vaccines if the US market is not available. However, she added, “I also met investors who don’t care because they say, ‘Okay, the policy will change again, and until we are in the clinics we don’t care.’”
Indeed, Protzer said, “I’m still convinced if I can reach something with mRNA vaccines, which I cannot with another platform, people will apply it.” Another group of researchers from institutions outside of the US expressed the importance of continuing work in mRNA technology even with the potential absence of US support, citing its flexibility for epidemics and the potential to improve protection against new or difficult pathogens. They called for identifying new funding sources, investing in foundational science, and addressing misinformation as some key areas to promote this research abroad.
Loss of Support for mRNA Will Slow, but Not Stop, Scientific Advancements
Even with the hurdles, mRNA vaccine research hasn’t completely stopped in the US either. Despite the loss of BARDA funding, Moderna, in partnership with researchers at the University of Texas Medical Branch, is continuing work on their mRNA vaccine against Marburg virus. Carfi said that the work has continued by acquiring funding from other sources, although those are not necessarily as robust as that from the BARDA program.
Additionally, a spokesperson for Moderna said that a previously announced plan to progress their seasonal vaccine platforms, including their influenza vaccine, is still active. The company recently published the positive findings from its Phase 3 clinical trial of this vaccine, boding well for that strategy.12 The spokesperson said that these products and their pipeline will go on to support future work in cancer vaccines and those against rare diseases. “I’m very excited about things that we’re already doing, but I’m also excited where the technology is going,” Carfi said.
He added that, to some extent, research has always seen this type of increasing and decreasing funding, especially for vaccines. Current events have previously guided scientific efforts in a specific topic. Fuller agreed, pointing to the interest in coronavirus research in the early 2000s after the first SARS virus. Although a lot of the funding ebbed as the epidemic passed, much of the basic science research that continued laid important groundwork that helped efforts for COVID-19 responses.
Fuller said that the current US administration’s stance against mRNA will likely have a dampening effect on mRNA research in the US. At the same time, though, she said that mRNA technology is out of the figurative bottle. “That magic is happening somewhere in the world,” Fuller said. If the US chooses to not invest in mRNA research and vaccines, then, she added, “Our next vaccine against the next pandemic may not come from the scientists here. It may come from somewhere else.”
Many scientists, like herself, she added, will probably pivot as they have in the past to focus on more foundational biology. For example, she said that her group is currently exploring the potential to design an mRNA vaccine against a fungus.
However, she said that, in addition to the retracted mRNA vaccine funding, many other recent decisions from the current administration, for example the proposed cuts to basic science funding, feel like the support for science overall is eroding. This leads to more struggles for biomedical research, making it harder for scientists to continue foundational research and pivot to new areas, which could have long-term impacts on the development of new technologies and insights.
At this time, it’s too early to anticipate the downstream effects from the US’s lost mRNA vaccine support on research and public health. Although agencies like the FDA have indicated continued interest in mRNA technology for cancer and rare disease therapies, Fuller pointed out that, because scientific innovations often cross over into other disciplines, limiting mRNA vaccine research in this way could delay advancements in other research areas.
Yet scientists at Arcturus Therapeutics remain optimistic about the potential for mRNA in therapeutics, despite the current climate surrounding mRNA vaccines. A spokesperson shared that the company’s current focus is on leveraging mRNA for protein replacement therapies, and that recent policies and changes in support for mRNA vaccines haven’t changed their goals. The representative shared that the company sees mRNA transitioning from “primarily a pandemic-response tool into a foundational therapeutic modality,” where it can offer treatments for rare diseases and other conditions that have limited current options. They added that, for therapeutics, mRNA remains a strong potential option.
Yet, restricting work in preventative vaccines for pathogens could undermine the ability to directly address other conditions at their source. For example, Gronvall said that researchers are finding more cancers and diseases, like hepatocarcinoma and multiple sclerosis, have infectious origins. Even if policies change in future administrations, Gronvall said, “I worry that it’s going to take a generation literally to be able to recover some of what has been lost in the last year.”
Fuller echoed these concerns and explained that she’s worried about how these changes are affecting early career researchers’ decisions about what fields to pursue. But, she added, “This technology is here to stay. It’s going to have a huge influence and impact in the future. Nobody’s going to stop that—no administration, no ideology. Science will go forward somewhere and somehow.”
Shelby Bradford is an Associate Editor at The Scientist. She earned her PhD in immunology and microbial pathogenesis from West Virginia University, where she studied neonatal responses to vaccination. Find Shelby on X @TheGeekyGoth
A version of this article was originally posted at The Scientist and is reposted here with permission. Any reposting should credit both the GLP and original article. Find The Scientist on X @TheScientistLLC
