Topline
The first mRNA mpox vaccine to be pitted against licensed vaccines beat its rivals by easing symptoms and potentially cutting transmission, according to new research published Tuesday, a coup for manufacturer Moderna as it strives to prove itself beyond COVID-19 amid efforts to contain an escalating outbreak of mpox in Africa.
Key Facts
The peer reviewed study, published in the journal Cell, marks the first time an mRNA vaccine has been directly compared to the already-licenced shot, Bavarian Nordic’s modified vaccinia Ankara (MVA) vaccine, sold under brand names Jynneos, Imvamune and Imvanex, in nonhuman primates, said Moderna virology researcher and author Alec Freyn.
To test the two shots, researchers from Moderna, the United States Army Medical Research Institute of Infectious Diseases (USAMRIID), the National Institute of Allergy and Infectious Diseases and Boston University gave each vaccine to six macaques, exposing them to a lethal strain of the virus eight weeks later and monitoring their health and blood for signs of an immune response for another month.
All animals vaccinated with Bavarian Nordic’s MVA shot and Moderna’s experimental vaccine, mRNA-1769, survived the trial, while five of the six macaques in an unvaccinated control group died from the disease, researchers said, and the Moderna group had higher numbers of antibodies in blood samples, suggesting a stronger immune response.
As well as preventing lethal infections, the researchers said Moderna’s investigational vaccine reduced disease severity compared to the licensed shot—mRNA-immunized macaques had a maximum of 54 mpox lesions compared to 607 in the Bavarian group and 1,448 in the unvaccinated group—and shortened disease duration by more than 10 days.
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Macaques in the mRNA group also had lower amounts of the mpox virus in both their blood and throat swabs, suggesting Moderna’s vaccine could also be effective at reducing virus transmission.
“With the mRNA technology, we’re able to produce a vaccine that gives quite potent responses with a very tolerable safety profile,” said senior author Jay Hooper, a virologist at USAMRIID, adding that an mRNA shot could help prevent the disease spreading without the safety issues that prevent widespread use of some other vaccines used for mpox, such as Emergent BioSolutions’ smallpox shot ACAM2000.
Key Background
Mpox, formerly known as monkeypox, is a viral illness caused by infection with the monkeypox virus. In August, the World Health Organization declared a growing outbreak in central Africa a public health emergency of international concern. It is the second time the agency has made such a warning, the highest level of alert it can sound under international law, in as many years, following a global outbreak in 2022. That outbreak, which predominantly affected gay, bisexual and other men who have sex with men, was driven by a different and milder variant behind the outbreak we are seeing now, which data suggests could kill as many as 10% of people it infects. Young children, pregnant people and those with compromised immune systems are particularly at risk and symptoms of infection include a fever, swollen lymph nodes and characteristic, pus-filled rash. The virus spreads primarily through close contact with infected people, animals or contaminated materials like towels and while the variant was historically limited to small outbreaks in central Africa, it appears to have mutated into a more transmissible form.
News Peg
The Africa Centers for Disease Control and Prevention said there have been at least 17,500 cases and 517 deaths from the virus in 2024 alone, though officials acknowledge surveillance is limited and warn the figure is potentially much higher. Amid ongoing outbreaks of the clade IIb virus variant responsible for the 2022 global outbreak, a handful of clade Ib infections have since been reported outside of Africa, including in Sweden and Thailand, though most are still located within the Democratic Republic of Congo and nearby countries. While there are a number of authorized vaccines for use against mpox, constraints like cost, availability or suitability have hindered widespread uptake. Supplies of the preferred shot, Bavarian Nordic’s MVA vaccine, are limited, for example, and it is relatively expensive and has limited effectiveness at reducing the severity of symptoms and curbing transmissibility. Emergent’s ACAM2000, on the other hand, is in plentiful supply due to stockpiling against a potential smallpox threat and can cut the risk of transmission effectively but the risk of severe side effects may make widespread use inappropriate.
What To Watch For
The tests Moderna are conducting in nonhuman primates are being run alongside tests in humans. The company’s mRNA-1796 shot is being assessed in an early stage clinical trial to determine safety, tolerability and immune response over a range of doses. The outcomes of this will determine the trajectory of future trials for the vaccine.
How Do Mrna Vaccines Work?
Vaccines train your body to fight off pathogens in a safer way than if they were encountered naturally. This involves presenting the immune system with something it would later recognize and respond to if encountered at a later date, giving it a head start to help prevent infection entirely or reduce disease transmissibility and the severity of symptoms. Most vaccines make use of a weakened or inactivated (killed) version of the disease-causing germ, or a specific part of the germ like a protein or sugar, to spark an immune response, which impose limits on how fast a new shot can be developed and scaled up. mRNA shots work by providing instructions to the body allowing it to produce part of the germ itself, triggering an immune response without needing any exposure to the germ. By nature, mRNA shots can be more flexible and specific than shots using the entire virus.
Can Mrna Vaccines Help Tackle Emerging Pandemics?
The swift development, testing and approval of mRNA vaccines during the COVID-19 pandemic was a landmark moment for public health and the first time mRNA shots had been authorized after decades of struggles and setbacks. The scalability of mRNA vaccines outpaced more traditional methods, illustrating why experts now believe the technology platform will be a crucial tool for tackling emerging pandemic threats. Many experts and health groups like the World Health Organization and the Coalition for Epidemic Preparedness Innovations (CEPI) flag diseases like bird flu, Nipah, Lassa Fever, Ebola and Marburg, Zika, coronaviruses like COVID-19, SARS and MERS and Rift Valley fever as urgent priorities for research given their high potential to seed future pandemics and the absence of countermeasures. Meanwhile, some experts have long warned one of humanity’s greatest public health achievements—the eradication of smallpox through a highly successful vaccination campaign—has potentially left the world vulnerable to outbreaks of related diseases that can exploit our lack of immunity now that we no longer immunize ourselves against it. Mpox, an Orthopoxvirus like smallpox virus variola, is one such threat, and there are many other viruses in the group like camelpox, Alaskapox, cowpox, rabbitpox, dolphinpox and horsepox, some of which are known to infect humans and for which the risks are Blood serum from vaccinated macaques “neutralized not only mpox but also vaccinia, cowpox, rabbitpox, camelpox, and ectromelia virus,” Freyn said, a sign the vaccine would convey at least some protection against the virus. “We believe that this vaccine may protect from other Orthopoxvirus threats that may emerge in the future,” he said.
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