The emergence of a second mpox outbreak in which the virus is spreading from person-to-person, as well as a sharp increase in overall cases of the disease in several African countries, is straining the world’s capacity to make and distribute vaccine to battle the threat. New options are needed, and a study published Wednesday suggests another may be on the horizon.
The vaccine manufacturer Moderna reported in the journal Cell that a messenger RNA-based mpox vaccine that it is developing was more protective than a vaccine made using the same platform as Bavarian Nordic’s Jynneos vaccine in a study in which non-human primates were vaccinated, then deliberately infected with mpox.
All the animals vaccinated with either vaccine survived what would otherwise have been a lethal challenge with an injection of the mpox virus, the study reported. But four of six primates that received the vaccine formulated to mimic the Jynneos vaccine nevertheless went on to develop enough lesions to meet the World Health Organization’s criteria for “grave” disease (more than 250 lesions).
None of the macaques that were vaccinated with the experimental Moderna vaccine, mRNA-1769, even developed “severe” disease (more than 100 lesions).
“We could see how this vaccine not only provided different levels of immunity, but also provided direct protection from a lethal, intravenous challenge of [mpox] virus,” Alec Freyn, an author of the study and Moderna’s preclinical research lead for mpox vaccine development, told STAT in an interview.
The vaccine targets four proteins that are found in all known poxviruses and that are critical to the life cycle of poxviruses, said Galit Alter, Moderna’s vice president for immunology research and a senior author of the study. Whereas other mpox vaccines use whole, weakened viruses to generate protection, mRNA-1769 focuses the immune response on these four key targets, the Moderna scientists said.
Krutika Kuppalli, a former WHO scientist who worked on mpox at the agency, welcomed the findings.
“The data on Moderna’s mRNA-1769 vaccine is a promising development,” she said in an email. “The faster resolution and milder disease in the mRNA-1769 group not only underscores the vaccine’s ability to mitigate infection but also suggests potential for reducing onward transmission by shortening the infectious period.”
The existing approved mpox vaccines — Bavarian Nordic’s Jynneos, KM Biologics’ LC16, and Emergent’s ACAM2000 — are made using a modified vaccinia Ankara virus (MVA). It is a live but weakened virus that is a member of the poxvirus family and offers protection against related viruses. In addition to being used to protect against mpox, MVA-based vaccines are also stockpiled as a hedge against a bioterrorism attack involving the smallpox virus, a more dangerous poxvirus that was declared eradicated in 1980.
ACAM2000 cannot be given to people who are immunocompromised, which would make this vaccine’s deployment challenging in places where people are living with poorly or uncontrolled HIV.
A trial to determine mRNA-1769’s safety, tolerability, and ability to trigger an immune response in people is underway in the United Kingdom. That Phase 1/2 trial, which enrolled 350 people, began last year. Some results may be available before the end of this year, or in 2025, Moderna said.
In late August the WHO declared a surging outbreak of mpox in Africa a public health emergency of international concern, the second time the virus has triggered a so-called PHEIC in two years. Last week the global health agency unveiled a six-month plan to battle transmission of the virus.
Mpox, which is endemic in parts of west and central Africa, is harbored by some rodents and possibly other small animals. When people become infected, they develop raised, pus-filled lesions that eventually scar. Most people survive but the disease can be deadly, especially in young children and people with compromised immune systems.
Historically infections occurred in people — often children — who trapped and handled infected animals, with some limited spread within households or communities.
But in 2022, cases of mpox were diagnosed in the U.K. in people who had not traveled outside the country. Investigation of those infections revealed that the virus had been spreading person-to-person, likely for several years, largely among gay, bisexual, and other men who have sex with men. That outbreak quickly spread to multiple countries in Europe, North America, and beyond.
Behavioral change within affected communities and use of vaccines in some countries tamped down spread considerably. But transmission from that outbreak continues to this day, with more than 120 countries reporting nearly 103,000 cases and 223 deaths since 2022. The United States has reported the largest share of those cases — more than 32,000 cases and 58 deaths.
Last fall the Democratic Republic of the Congo detected person-to-person transmission of a different strain of mpox in the eastern part of the country, among sex workers, their clients, and men who have sex with men. (There are two strains, known as clades, of mpox virus.) Cases linked to that outbreak have been reported in Burundi, Kenya, Rwanda, and Uganda as well as Sweden and Thailand. (The cases in Sweden and Thailand were related to travel to Africa.)
Moderna’s vaccine is not currently licensed or even authorized for emergency use. Even if all goes well with the Phase 1/2 trial in the U.K., it will take some time before the vaccine could be used in the field. But it is clear from the past few years that the mpox threat is not going away, and that existing capacity to make vaccine to protect against it is too limited. And the response to the Covid-19 pandemic showed that scaling up production is easier for mRNA vaccines than it is for vaccine production that is based on growing stocks of virus, as MVA vaccine production is.
“The production delays with [the Bavarian Nordic vaccine] during the global outbreak, which continue as mpox cases rise in Africa, underscore the importance of having multiple vaccines produced through different methods,” Kuppalli, an infectious diseases specialist, said. “From our experience with Covid-19, we know that mRNA vaccines are both safe and quickly scalable, which is an additional advantage should the virus continue to evolve.”