The commonly used mpox vaccine offers only partial immunity and does not completely prevent serious symptoms or the spread of the disease. However, Moderna’s new vaccine candidate, mRNA-1769, has demonstrated better effectiveness in alleviating symptoms and shortening the duration of illness in primates infected with a deadly strain of the mpox virus, outperforming the existing licensed modified vaccinia Ankara (MVA) vaccine.
The commonly used mpox vaccine offers only partial immunity and does not completely prevent serious symptoms or the spread of the disease. However, Moderna’s new vaccine candidate, mRNA-1769, has demonstrated better effectiveness in alleviating symptoms and shortening the duration of illness in primates infected with a deadly strain of the mpox virus, outperforming the existing licensed modified vaccinia Ankara (MVA) vaccine. The study was published on September 4 in the journal Cell by Cell Press.
“This study is the first to directly compare an experimental mRNA mpox vaccine to the current standard of care in a nonhuman primate model,” explains co-first author Alec Freyn, a virology researcher at Moderna. “When we placed these vaccines side by side in primates, the mRNA vaccine showed better outcomes not only in survival rates but also through fewer lesions, a shorter illness duration, and reduced viral shedding in both blood and respiratory samples.”
MVA vaccines, initially developed to fight smallpox, consist of live but weakened viruses that cannot cause disease in humans. This attenuation, however, limits their protective capabilities compared to other vaccines like the ACAM2000, which can be effective but carries risks of infection. In contrast, the mRNA technology allows for the creation of vaccines that include only the components of the virus most effective in triggering a strong protective immune response without the risk of encountering a full infectious virus. The investigational mpox mRNA vaccine contains four vital viral antigens essential for the virus’s ability to bind to and enter host cells.
“By utilizing mRNA, we can select specific parts of the virus that elicit the strongest immune response,” states senior author Galit Alter, a virologist and immunologist at Moderna. “This focused approach lets us concentrate on key viral components crucial for protection rather than being distracted by the entire virus.”
Although earlier research has indicated that mRNA vaccines can avert lethal mpox infections in nonhuman primates, their effectiveness in reducing disease severity had not previously been evaluated. To rigorously compare the investigational mRNA vaccine with MVA vaccines, the researchers immunized six macaques with each type of vaccine and exposed them to a dangerous strain of mpox virus eight weeks post-vaccination. A control group of six unvaccinated primates was also exposed to the virus. After infection, the health of all animals was monitored for four weeks, and blood samples were collected to analyze their immune responses.
All twelve vaccinated primates survived the infection challenge, regardless of the vaccine used, while five out of six unvaccinated control primates did not survive. Though both vaccines lessened disease severity in comparison to the controls, animals receiving the mRNA vaccine lost less weight and showed fewer lesions than those vaccinated with MVA. On average, the control group displayed a maximum of 1,448 lesions, MVA-vaccinated animals experienced up to 607 lesions, while the mRNA-vaccinated animals had a maximum of only 54 lesions. Furthermore, the mRNA vaccine considerably reduced the duration of illness (the time animals exhibited lesions) by over 10 days compared to the MVA vaccine, and it resulted in lower viral loads in both blood and throat samples, which may help curb transmission.
“With mRNA technology, we can create a vaccine that triggers robust responses while maintaining a favorable safety profile,” says senior author and virologist Jay Hooper of the United States Army Medical Research Institute for Infectious Diseases. “We’ve aimed to produce a vaccine that can prevent the spread like ACAM2000® but without the associated safety challenges. This research indicates that mRNA technology could fulfill that need.”
The researchers found that the immune response generated by the mRNA vaccine was stronger than that generated by the MVA vaccine, resulting in a greater number of antibodies and a wider array of immune functions. The team identified various types of antibodies linked to improved viral control and reduced lesions.
Additionally, the mRNA vaccine showed promise in eliciting cross-immunity against other Orthopoxviruses, while the MVA vaccine elicited smaller immune responses that were less effective at neutralizing more distantly related members of the same virus family.
“We tested serum from the monkeys immunized with this vaccine against practically every Orthopoxvirus we could find,” remarks Freyn. “It was able to neutralize not just mpox but also vaccinia, cowpox, rabbitpox, camelpox, and ectromelia virus. We believe this vaccine could provide protection against other Orthopoxvirus threats that may arise in the future.”
Currently, Moderna’s mRNA-1769 vaccine is undergoing a phase 1/2 clinical trial (NCT05995275) aimed at assessing the safety, tolerability, and immune response of multiple doses of mRNA-1769.
