Safety, effectiveness, speed: Experts highlight benefits of mRNA vaccines

Vaccines have saved millions of lives and that medical technology will get better as researchers continue working with messenger RNA (mRNA) to find faster ways to prevent illnesses, said two experts who spoke about inoculations for patients.

Two Johns Hopkins Bloomberg School of Public Health researchers made the case for continued investment in messenger RNA (mRNA) vaccine technology. While there may be physician concerns about patient safety and public skepticism rooted in misinformation, loss of federal support could slow progress in the science of vaccines, said Andrew Pekosz, Ph.D., and Gigi Gronvall, Ph.D. They discussed the science behind the shots during an online briefing with news media on March 26.

How mRNA vaccines work — and why speed matters

Pekosz opened by distinguishing mRNA vaccines from traditional shots.

Conventional non-replicating vaccines, such as the standard influenza vaccine, work by introducing a known quantity of a foreign protein and prompting the immune system to respond, said Pekosz, professor and vice chair of the W. Harry Feinstone Department of Molecular Microbiology and Immunology. He also co-directs the Johns Hopkins Center of Excellence in Influenza Research and Response.

He noted MRNA vaccines work differently by delivering genetic instructions that direct the body's own cells to produce a foreign protein, triggering a broader and faster immune response.

“They introduce a molecule called an mRNA that is coding this foreign protein, and it's actually the cells in your own body that make that foreign protein and that starts to stimulate the immune system to recognize it,” Pekosz said. “And it's that ability to express that foreign protein inside your cells that oftentimes make up makes mRNA vaccine technology so effective, it almost shows your body that an infection without having the really dangerous parts of a virus, for instance, as part of the process of generating that immune response.”

The mRNA shots also can be produced much faster than traditional vaccines, a key advantage for patient health. Pekosz compared the shift from conventional vaccine production to mRNA technology to going from a horse and buggy to a Corvette; both get to the same destination, but the sports care is far faster.

That speed has particular implications for influenza, Gronvall said. Current flu vaccines must be manufactured five to six months before flu season begins. That requires global health experts, including those at the World Health Organization and the Centers for Disease Control and Prevention, to predict circulating strains well in advance, usually starting in February preceding the flu season expected later the same year.

By comparison, mRNA flu vaccines can be manufactured in under two months. That compressed timeline would allow health authorities to observe circulating strains closer to flu season before committing to a formulation, improving the match between the vaccine and the viruses people are likely to encounter.

Regardless of the timing, Gronvall encouraged physicians and patients to get a flu shot in the fall.

"Even in those years that there is a bit of a mismatch between the virus and what the flu vaccine protects against, I want to be very clear that everyone should get a flu shot every year," Gronvall said. "But with mRNA, the hope is that it will be even more effective at reducing sickness, hospitalizations and deaths."

Pekosz noted an additional technical limitation of current flu vaccines: most are manufactured in eggs, a process that can introduce mutations making the final product a less accurate match to circulating strains. MRNA vaccines would be built entirely from the genetic sequence of the target virus, bypassing that problem.

Addressing vaccine misinformation

During the worst parts of the COVID-19 pandemic, people began hearing falsehoods about mRNA vaccines and those have remained in patients’ minds, Gronvall said. Primary care physicians should remember those to explain to their patients who may be skeptical or fearful.

"MRNA vaccines do not hang around in your body for long. They do not get incorporated into your DNA," she said. She also flatly rejected claims that mRNA vaccines cause cancer — a claim sometimes referred to as "turbo cancer" online — and said the technology has no effect on fertility.

Gronvall emphasized that the foundational science behind mRNA vaccines had been in development for years before the pandemic. Katalin Karikó and Drew Weissman of the University of Pennsylvania, whose research was published in 2005, won the 2023 Nobel Prize for physiology or medicine for their work on mRNA modifications that made the vaccines possible.

On efficacy, at least one analysis estimated mRNA COVID-19 vaccines saved more than 14 million lives worldwide in their first year of rollout, Gronvall said. She noted that the toll of hospitalizations prevented was even larger, and urged physicians not to underestimate the physical and psychological burden of serious illness.

“And people should remember that you don't just bounce right back after being in the hospital. Being intubated, it's a very disorienting experience. It's not fun at all,” she said. “And so these vaccines save people so much pain and suffering, not to mention economic loss.”

More about side effects

Pekosz addressed the side effect profile of mRNA vaccines, noting that most are driven by the strength of the immune response itself, which causes fatigue, localized redness and body aches lasting a day or two. He acknowledged that myocarditis, or inflammation of the heart muscle, was observed in a small percentage of young males who received mRNA COVID-19 vaccines, but was clear about the greater risk caused by the virus.

"The rate of myocarditis from COVID-19 infection was significantly higher than that from vaccination," he said. "Even with those side effects, the vaccines give you lower side effects than the actual infection."

Newer generations of mRNA vaccine platforms are specifically designed to reduce side effects while maintaining efficacy. “This technology is not frozen, and it is constantly evolving, and some of the concerns that people voice about wanting something with less side effects or with more efficacy are actively being investigated by both academic laboratories as well as by companies,” he said.

Cancer applications and personalized medicine

When asked about mRNA vaccines for cancer, Pekosz drew a distinction between preventive and therapeutic uses. The most advanced applications currently involve therapeutic vaccines designed for patients who already have cancer and that target proteins expressed on cancer cells. He described early-stage research into personalized cancer vaccines that would be custom-designed to match the specific proteins a patient's tumor is displaying.

"A physician could go in, test your cancer, find some of the unique proteins that those cancers are showing, and then design a personalized mRNA vaccine that can target your specific cancer," Pekosz said. He noted that while most of this work is still in early development, it represents a promising frontier.

Gronvall added that existing vaccines against hepatitis B and the human papillomavirus (HPV) already prevent cancer. “There is every reason to think that mRNA will be used as a platform for those for both of those cancers, to prevent those cancers and possibly others,” leading to a bright future in medicine, she said.

Federal support, bird flu and global equity

Both researchers expressed concern about the current federal posture toward mRNA technology. Pekosz said progress on mRNA vaccines for infectious diseases would slow without robust National Institutes of Health (NIH) basic research support. He noted the Food and Drug Administration has signaled continued support for mRNA cancer treatments, which he described as a positive sign.

Gronvall was more critical on pandemic preparedness, calling the cancellation of a federal contract for an mRNA vaccine against H5N1 avian influenza a "strategic mistake." She noted that H5N1 bird flu is already endemic in the United States and is causing significant disruption in the agricultural sector, making the risk of human-to-human transmission a live concern even if the timing remains unpredictable.

She also challenged comments by NIH Director Jay Bhattacharya, M.D., Ph.D., who she said cited public distrust as a reason to invest in older, less efficient vaccine technologies. "His job is to create trust in the proven technologies that will help save lives, and giving Americans a less effective product will not help to do that, especially if people see that mRNA vaccines that are more effective are available elsewhere in the world."

On global equity, the COVID-19 pandemic demonstrated both the power of mRNA technology and the inequality of its distribution, Gronvall said. She pointed to organizations including the WHO and the Coalition for Epidemic Preparedness Innovations (CEPI) as essential to ensuring that future mRNA-based vaccines reach lower-income countries.

"Infectious diseases famously do not stick to borders," she said.