Moderna's mRNA vaccine candidate, mRNA-1769, has shown promising results in a preclinical study, demonstrating superior protection against mpox compared to the Bavarian Nordic Jynneos vaccine. The study, published in Cell, highlights the potential of mRNA technology in combating the emerging clade Ib strain of the virus, which has been spreading across African countries, particularly in the Democratic Republic of Congo.
The trial involved three groups of monkeys, each with six animals. One group received mRNA-1769, another received Jynneos, and the third received a placebo. The subjects were dosed twice, with the second dose administered four weeks after the first, and were evaluated daily for 12 weeks. The results indicated that mRNA-1769 was more effective in preventing severe disease and reducing virus levels.
Enhanced Efficacy and Reduced Viral Replication
The mRNA-1769 vaccine not only prevented severe disease but also significantly reduced viral replication in the blood and throat of the monkeys. This reduction in viral load is crucial, as researchers believe it could lead to both disease modification and a decrease in the potential for viral spread. Furthermore, the vaccine led to reduced lesion formation, a hallmark of mpox infection.
According to Moderna virologist and study coauthor Alec Freyn, the improved protection was enabled by a strong, vaccine-induced antibody response. "We're able to provide those antigens in such a way that they're able to stimulate an incredibly potent immune response," Freyn stated.
mRNA Technology for Rapid Response
One of the key advantages of mRNA technology is its flexibility and speed in vaccine development. Peng George Wang, a biochemist at the Southern University of Science and Technology, noted that scientists can quickly update the mRNA blueprint to address variant virus strains. Moderna's candidate, mRNA-1769, uses four proteins detected in the mpox virus to mimic the virus, triggering the body to create antibodies to tackle the virus.
Clinical Trials and Future Directions
Moderna is currently conducting a Phase I/II clinical trial (NCT05995275) of the mpox vaccine in healthy participants in the UK. The trial has fully recruited approximately 350 participants across several sites in the UK, who were chosen at random to receive two doses of the investigational vaccine or a placebo. The trial will last approximately 13-14 months, with data expected in mid-2025. This data will be crucial in shaping the design of a Phase III trial.
A Moderna spokesperson stated, "Moderna is investigating a potential vaccine for mpox and smallpox in a Phase I/II Study conducted in the UK."
Comparison with Existing Vaccines
The current mpox vaccine, Jynneos, is a modified vaccinia Ankara (MVA) vaccine that uses a weakened version of the vaccinia virus. While effective in preventing death, it has limitations, including incomplete immunity and unclear efficacy against more virulent clade I strains. The mRNA-1769 vaccine offers a potential alternative with improved protection and the ability to adapt to emerging strains.
It is important to note that a study published earlier this year by BioNTech showed that their mRNA vaccine, BNT166, protected macaques from disease. However, that study did not use an MVA comparison vaccine.
While Moderna’s vaccine used a much higher dose than BNT166, which could raise the risk of side effects, Galit Alter from Moderna said that they calculated the current dose “so that we can really lend and drive the highest level of immunity to those individuals that are really on the front line.” Freyn said that the team is currently conducting dose de-escalation studies. “We may be able to find that balance between great immune responses, but also a better, more tolerable reactogenicity profile,” he added.
