mRNA Helped Quell COVID-19 but COVID-19 ‘Maimed’ mRNA

Messenger RNA was meant to meet the moment in 2020.

In 2002 and 2003, the SARS-CoV-1 virus issued a shot across the bow. While it never really gained traction in the U.S., work toward an mRNA vaccine ramped up, and when SARS-CoV-2 exploded across the globe almost 20 years later, the technology was ready to save some 3 million American lives.

“We were well poised to make an mRNA vaccine,” Paul Offit, director of the Vaccine Education Center at Children’s Hospital of Philadelphia, told BioSpace.

This is, by most accounts, a quintessential success story of scientific innovation. But the story has taken a dark turn.

“It became political,” Offit said. “Highly political.”

Recently, the Department of Health and Human Services, under President Donald Trump and Secretary Robert F. Kennedy Jr., has threatened to cut funding for mRNA research. In February, reports emerged that the government was re-evaluating a $590 million contract issued by the previous administration to Moderna for an mRNA-based bird flu vaccine. And in March, KFF Health News reported that National Institutes of Health officials encouraged scientists to remove all references to mRNA vaccine technology from their grant applications.

For the current administration, these moves reflect a larger anti-vaccine sentiment perpetuated by Kennedy. For mRNA, in particular, experts say there could be lasting consequences to a promising field of research that goes far beyond vaccines.

During the pandemic, “people like RFK Jr. . . . [were] out on the airways saying, ‘this COVID vaccine is the most dangerous vaccine ever made,’” Offit recalled. “So [mRNA] became a victim of disinformation, and a victim of sort of the political zeitgeist, which was to push back on vaccines.”

As for the pandemic’s overall impact on mRNA as a field, Offit said: “I think it didn’t kill it. I think it maimed it for a little while.”

Joseph Payne, CEO of mRNA company Arcturus Therapeutics, took a more optimistic stance. “I think COVID did an extraordinary job to accelerate not only conventional mRNA technology but the next-generation technologies as well,” he told BioSpace.

The two mRNA-based COVID-19 vaccines—Comirnaty, developed by Pfizer and BioNTech and Moderna’s Spikevax—were “highly effective against severe disease, and efficacy against severe disease lasted,” Offit said, adding that mRNA vaccines were estimated to have saved around 3 million lives in the U.S. As a result, in 2023, Katrina Karikó and Drew Weissman, both of the University of Pennsylvania, won the Nobel Prize for their foundational research that paved the way for mRNA-based vaccines and therapeutics.

The anti-vaccine rhetoric espoused by Kennedy and others during the pandemic wasn’t—and isn’t—being inflicted by one man, or one administration. Offit acknowledged that during the early days of the pandemic, healthcare leaders “tended to oversell [the mRNA vaccines] to some extent.”

During 2021, “you were 12 times more likely to be hospitalized and 12 times more likely to die from COVID if you weren’t vaccinated, and so we really pushed that vaccine,” Offit said. “I think we weren’t good at talking about what it could and couldn’t do,” such as its ability to prevent severe disease vs. a milder infection. “So, I think that was a problem.”

Adding to the societal case against mRNA is that it can be a “tough vaccine” in terms of relatively minor side effects, Offit said, including lymph node swelling and fever.

It was also a first-in-class mechanism. While most vaccines include an attenuated form of the virus or a single protein, mRNA vaccines provide a gene that codes for the spike protein on the surface of SARS-CoV-2. “So it was a, quote, unquote, genetic vaccine, and I think when people hear that, they think it’s going to affect their own genes,” Offit said. mRNA vaccines have been alleged to enter DNA and cause cancer, a contention Offit called “utter nonsense.”

Today, as HHS Secretary, Kennedy continues to scrutinize vaccines. Last week, the FDA introduced new risk-based approval requirements for future COVID-19 candidates, and at a U.S. Senate hearing earlier this month, Kennedy declined to recommend the measles vaccine after previously endorsing it. Kennedy’s long-term fight against vaccines also featured prominently in a MAHA report released by the White House last week.

In an emailed statement to BioSpace, a Moderna spokesperson said this misperception of mRNA has led to actions by state governments against the use of the technology. In March, ABC News reported that legislation aimed at banning or limiting mRNA vaccines was introduced this year by GOP lawmakers in at least seven states, with some congressional Republicans even encouraging regulators to pull federal approval for mRNA-based COVID vaccines. And last month, eight Republicans in the Minnesota House introduced legislation that would designate certain vaccines and medical treatments—particularly mRNA-based products—as “weapons of mass destruction.” Possessing or distributing these treatments would be a crime, punishable by up to 20 years in prison.

“Legislative efforts to ban or restrict mRNA medicines in various states are largely driven by misunderstandings about their well-established safety profile and mechanism of action,” the Moderna spokesperson said. “For example, while mRNA does not modify DNA, this misconception is frequently cited in support of such policies.”

“If enacted, these measures could hinder important research and limit patient access to innovative treatments, potentially delaying life-changing medical advancements,” the spokesperson added.

Offit echoed this sentiment. “There’s a lot of tragedies in this,” he said, one of the biggest being impacts on research into other applications like a universal flu shot, malaria and tuberculosis vaccines, as well as cancer therapeutics. “I worry that we’re going to lose that.”

But all is not bleak, according to Payne, who noted that Arcturus received Fast Track Designation from the FDA in April for its self-amplifying mRNA pandemic influenza A virus H5N1 (bird flu) vaccine. “If [the U.S. government] were trying to slow things down, they wouldn’t be fast-tracking our technology,” he said.

Self-amplifying mRNA is a “considerably lower dose technology,” with injections at 5 mg as opposed to the 50–200 mg used with first-generation mRNA technologies, Payne explained. This confers benefits in terms of safety, reactogenicity and cost of goods.

Payne said that while there has been a reduction in funding for first-generation mRNA technology, “on the next-gen technology, we haven’t seen any of that. Arcturus is developing mRNA therapeutics for two rare diseases, cystic fibrosis and ornithine transcarbamylase. The company announced earlier this month that it is scaling back work on its early-stage pipeline, which includes four investigational vaccines.

At Arcturus, “I think we would be disappointed or surprised if [the U.S. government] reduced funding on a potentially better, safer vaccine technology. . . . It would be surprising if some of those funds didn’t shift our way,” Payne said.

For Payne, the COVID pandemic’s influence on mRNA exists on a pendulum. “Just an extraordinary amount of data [was] collected in a very short period of time with multiple companies and multiple technologies,” he said. “If it wasn’t for COVID . . . there’d be no vaccines approved. We’d be swimming in early data still.”

Now, with the crisis in the rear-view mirror, “people are prosecuting and looking closely at different subsets of data,” he said. While there continues to be “elevated acceleration, now there’s elevated criticism.”

But this process of scientific analysis “only helps. It doesn’t hurt,” Payne added. As for the political landscape, he said, “These policies and politics can come and go, but good science will just stand true and strong and endure.”

Offit, however, was more reticent, maintaining: “I just fear that the mRNA technology is at risk.”