Moderna's mRNA Mpox Vaccine Promising in Monkey Trial

Current vaccines for mpox have been designed to combat smallpox, an older and rarer relative of the virus. However, new research from Moderna indicates that its new mRNA-based mpox vaccine might provide superior protection. The study's findings were published on September 4 in the journal Cell.

Galit Alter, a virologist and immunologist at Moderna, explained that the mRNA vaccine allows for the selection of specific viral components that elicit the strongest and most effective immune responses. This targeted approach offers better protection by focusing on the virus's most critical segments.

In July 2022, an mpox outbreak originating in Africa spread globally, affecting nearly 100,000 individuals, primarily gay and bisexual men, across 116 countries and resulting in approximately 200 deaths. The outbreak was mitigated by the timely use of the Jynneos vaccine and behavioral changes within the gay male community.

Recently, a new mpox outbreak has severely impacted central Africa, particularly the Congo. The Africa Centers for Disease Control and Prevention reported over 21,300 confirmed and presumed cases and 590 deaths across 12 countries, some of which had never been affected before. This underscores the need for new protective measures.

Current vaccines like Jynneos and ACAM2000 use weakened forms of a smallpox-like virus. While they offer some protection, their effectiveness against mpox is limited. Moderna’s new vaccine candidate, mRNA-1769, is designed to target the specific parts of the mpox virus that elicit strong, lasting immune responses.

In the recent study, Alter and colleagues compared the Moderna mRNA vaccine with the older vaccine in 18 macaque monkeys exposed to the mpox virus. The monkeys were divided into three groups: six received the older vaccine, six received the experimental mRNA vaccine, and six were left unvaccinated. After eight weeks, all monkeys were exposed to a potentially lethal strain of mpox, and their health was monitored for four weeks through blood samples and physical examinations.

The results showed that all 12 vaccinated monkeys survived mpox exposure, regardless of the vaccine used. However, those who received the mRNA vaccine experienced milder illness, losing less weight and developing fewer skin lesions. The mRNA-vaccinated monkeys had around 54 lesions each, compared to 604 in those given the older vaccine. Additionally, the mRNA-vaccinated animals had lesions for ten fewer days, indicating a reduced potential for virus transmission.

Blood tests revealed that the mRNA vaccine induced higher levels of antibodies and greater immune function diversity compared to the older vaccine. In contrast, five of the six unvaccinated monkeys succumbed to the virus.

Moreover, the new mRNA vaccine might offer broader protection against the Orthopoxvirus family, which includes mpox. According to Alec Freyn, a virology researcher at Moderna, the vaccine neutralized other viruses such as vaccinia, cowpox, rabbitpox, camelpox, and ectromelia in laboratory tests. This suggests that the vaccine could provide defense against future Orthopoxvirus threats.

The mRNA-1769 vaccine is currently undergoing a phase 2 human trial to evaluate its safety, tolerability, and immune response at various doses. The study on primates was funded by Moderna and the U.S. National Institutes of Health.

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