A new type of mpox, clade Ib, has been spreading rapidly within the Democratic Republic of Congo and leaking outside the African nation’s borders since Sept. 2023. In response, the World Health Organization (WHO) declared the outbreak a public health emergency of international concern (PHEIC) last month, the second such declaration for an mpox variant in the past two years.
The rise of mpox has sparked a mad dash to develop new vaccines that are safer, more effective and easier to manufacture. Moderna, a biotech best known for its mRNA Covid-19 vaccine, has aimed its expertise in the messenger molecules at mpox.
In a new study, Moderna’s mRNA vaccine candidate beat the dominant Jynneos vaccine at preventing severe disease and reducing virus levels in monkeys. The results were published in the journal Cell on Sept. 4.
“The mRNA-1769 vaccine appears promising,” Jean Nachega, M.D., Ph.D., an epidemiologist at the University of Pittsburgh who was not involved with the study, told Fierce Biotech in an email. “The vaccine’s ability to elicit a strong immune response, combining neutralizing and functional antibodies, suggests its potential as an effective tool against mpox.”
Moderna first saw the need and opportunity for a new mpox vaccine after the first PHEIC was declared in 2022, Alec Freyn, Ph.D., principal scientist in the biotech’s virology group, told Fierce in an interview.
“We started to advance preclinical development as quick as possible,” Freyn said, “and went from conception to a pivotal [non-human primate] study in half a year.”
Moderna’s vaccine candidate, mRNA-1769, contains mRNA molecules that code for four proteins found on the surface of the monkeypox virus (the virus itself is called monkeypox, while the disease the virus causes is mpox). Recipients’ bodies then turn the mRNA into viral proteins, which the immune system can learn to recognize and fight against.
The four chosen proteins are vital for the virus to replicate and are highly conserved across monkeypox’s relatives, the orthopox viruses. Freyn said the team has tested the vaccine in the lab against other orthopox viruses, like camelpox, rabbitpox and multiple mpox strains, and found it neutralizes them. “We think that we can protect against a broad range of orthopox viruses,” he said.
Freyn and colleagues put mRNA-1769 to the test in cynomolgus macaques, monkeys commonly used in animal studies. They randomized 18 macaques into three groups, with six monkeys each receiving Jynneos, mRNA-1769 or a saline solution control. After vaccination, the team injected the simians with a variant of mpox known to be lethal.
Five of the control macaques succumbed to the illness, while all of the vaccinated animals survived. Monkeys that received the mRNA vaccine showed the fewest lesions, a hallmark of mpox, with an average peak lesion count of 54. The Jynneos group had an average peak of 607, with all these macaques falling into the WHO’s classifications for severe disease (more than 100 lesion) or grave disease (more than 250 lesions). None of the mRNA vaccine recipients developed severe or grave mpox.
“We were very excited to see the mRNA vaccine performing quite well, especially in reducing the duration of disease and reducing the amount of lesions,” Freyn said.
But for Freyn, the most striking result is that the mRNA vaccine group had lower levels of monkeypox virus in their blood and throats compared to the Jynneos group. “I was definitely surprised by how well we were able to control virus in respiratory tissue,” Freyn said. “This is a nice additional piece of data that we can drive antibodies to the respiratory tract and potentially prevent transmission, but that will require additional study.”
“This reduced viral load could result in a lower risk of transmission, especially in at-risk populations,” Nachega said. “By controlling viral shedding, the vaccine could be a critical tool in limiting the spread of mpox.”
The team also found that exposure to mRNA-1769 led the macaques to produce antibodies that bound to the viral proteins stronger than antibodies produced by Jynneos. This may be because of the nature of the mRNA platform, Freyn said.
With the mRNA vaccine, the body is essentially told to focus solely on four key viral proteins; in contrast, Jynneos uses a weakened form of the monkeypox virus in its vaccine (a common technique), which means the immune system has to do more to decipher the right proteins to learn and target.
With its mettle tested in macaques, mRNA-1769 is now being put through a phase 1/2 clinical trial of 351 adults in the United Kingdom, with results set to read out by mid-2025.
An mRNA vaccine from Germany company BioNTech, BNT166, is also in clinical trials after previously proving it can protect mice and macaques from mpox. That company’s phase 1/2 trial, enrolling 64 people, is also set to wrap up by the middle of next year. At this point, there’s no way to directly compare Moderna’s vaccine to BNT166 or any other mRNA vaccines, Freyn said.