
Credit: Unsplash/CC0 Public Domain
The most frequently used mpox vaccine provides partial immunity to the disease but isn’t always able to prevent severe symptoms or disease transmission. A new vaccine candidate from Moderna, mRNA-1769, more effectively limits symptoms and disease duration in primates that were infected with a lethal strain of the mpox virus when compared to a currently licensed modified vaccinia Ankara (MVA) vaccine. The study was published September 4 in the journal Cell.
“This study is the first in a nonhuman primate model where we compare an investigational mRNA mpox vaccine directly to the current standard of care,” says co-first author Alec Freyn, a virology researcher at Moderna.
“When we put those vaccines head-to-head in primates, we saw improved responses from the mRNA vaccine in terms of not just protection from survival but also fewer lesions, shorter duration of disease, and less viral shedding in the blood and respiratory tract.”
MVA vaccines, which were originally developed to combat smallpox, contain whole viruses that have been weakened so that they cannot cause disease in humans. However, this weakening also means that they provide limited protection compared to other vaccines such as the potent but potentially infectious ACAM2000.
In comparison, using mRNA technology enables vaccines to be designed to include only the parts of the virus that are most likely to induce a lasting, protective immune response without exposing the person to a whole infectious virus. In this case, the investigational mpox mRNA vaccine is composed of four viral antigens that are critical for the virus to attach and enter host cells.
“With the mRNA vaccine, we’re able to pick pieces of the virus that can give the most potent and most effective immune response,” says senior author Galit Alter, virologist and immunologist at Moderna. “By doing that instead of being distracted by an entire virus, you’re able to narrow down on the pieces of the virus that give you protection.”
Though previous studies have shown that mRNA vaccines can prevent lethal mpox infections in nonhuman primates, their ability to limit disease severity hasn’t previously been tested.
To directly compare the investigational mRNA vaccine to MVA vaccines, the researchers vaccinated six macaques with each vaccine and then exposed them to a lethal strain of mpox virus eight weeks after their initial vaccine dose. They also exposed a control group of six unvaccinated animals to the virus.
Following infection, the researchers monitored the animals’ health for four weeks and collected blood samples to examine their immune response.
All 12 vaccinated animals survived the challenge, regardless of which vaccine was used, whereas five of six unvaccinated control animals succumbed to the disease.
Though both vaccines reduced disease severity compared to the control group, mRNA-vaccinated animals lost less weight and had fewer lesions than MVA-vaccinated animals—on average, animals in the control group had a maximum of 1,448 lesions, MVA-immunized animals had a maximum of 607 lesions, and mRNA-immunized animals had a maximum of 54 lesions.
The mRNA vaccine also shortened disease duration (the number of days for which the animals showed lesions) by more than 10 days compared to the MVA vaccine and resulted in lower viral loads in both blood and throat swabs, suggesting that it might also be more effective at reducing transmission.
“With the mRNA technology, we’re able to produce a vaccine that gives quite potent responses with a very tolerable safety profile,” says senior author and virologist Jay Hooper of the United States Army Medical Research Institute for Infectious Diseases.
“We’ve been trying to get a vaccine that will prevent spread like ACAM2000 but without the safety issues. This is showing that mRNA technology might be able to fill that niche.”
When the researchers compared the immune response triggered by the mRNA and MVA vaccines, they found that the mRNA vaccine resulted in higher numbers of antibodies, as well as antibodies with more diverse immune functions. The team was able to identify different classes of antibodies that were associated with enhanced viral control and fewer lesions.
The mRNA vaccine also showed potential to induce cross-immunity to other Orthopoxviruses, whereas the MVA vaccine results in smaller immune responses that are not as strongly neutralizing for more remotely related Orthopoxviruses.
“We tested serum from the monkeys immunized with this vaccine against basically every Orthopoxvirus we could get our hands on,” says Freyn. “It neutralized not only mpox but also vaccinia, cowpox, rabbitpox, camelpox, and ectromelia virus. We believe that this vaccine may protect from other Orthopoxvirus threats that may emerge in the future.”
Moderna’s mRNA-1769 vaccine is currently being assessed in a Phase I/II clinical trial (NCT05995275) to determine the safety, tolerability, and immune response of a range of doses of mRNA-1769.
https://medicalxpress.com/news/2024-09-mpox-mrna-vaccine-effectively-disease.html

Check out our mRNA service to expedite your vaccine research
PackGene Biotech is a world-leading CRO and CDMO, excelling in AAV vectors, mRNA, plasmid DNA, and lentiviral vector solutions. Our comprehensive offerings span from vector design and construction to AAV, lentivirus, and mRNA services. With a sharp focus on early-stage drug discovery, preclinical development, and cell and gene therapy trials, we deliver cost-effective, dependable, and scalable production solutions. Leveraging our groundbreaking π-alpha 293 AAV high-yield platform, we amplify AAV production by up to 10-fold, yielding up to 1e+17vg per batch to meet diverse commercial and clinical project needs. Moreover, our tailored mRNA and LNP products and services cater to every stage of drug and vaccine development, from research to GMP production, providing a seamless, end-to-end solution.
Related News
Navega Therapeutics Receives $4 Million CIRM Grant to Advance Epigenetic Gene Therapy for Chronic Pain
SAN DIEGO, CA – February 4, 2025 – Navega Therapeutics, a pioneering biotechnology company developing cutting-edge epigenetic gene therapies, today announced a significant milestone with the receipt of a $4 million Translational Science grant from the California...
Akribion Therapeutics Secures €8 Million in Seed Financing to Advance Novel RNA-Guided Cell Depletion Technology
ZWINGENBERG, Germany, February 4, 2025 – Akribion Therapeutics, a biotechnology company pioneering a unique, RNA-guided, nuclease-based technology for programmable cell depletion, today announced the closing of an €8 million Seed financing round. The round was led by...
UF-Kure19 CAR-T Cell Therapy Demonstrates High CR Rates, Low Toxicity in R/R NHL
Treatment with UF-Kure19, a rapidly manufactured CAR T-cell therapy, led to complete responses (CR) and low toxicity in patients with relapsed/refractory non-Hodgkin lymphoma, according to data from a single-arm, mult-center phase 1 study (NCT05400109) presented at...
Opinion: Companies Vie to Develop a Hunter Syndrome Therapy That Reaches the Brain
Several companies—including JCR Pharmaceuticals, Denali Therapeutics and Regenxbio—have products in the pipeline that could improve treatment options for this rare disease. Hunter syndrome is a rare, X‐linked disease caused by a deficiency of the lysosomal enzyme...
Related Services

AAV Packaging Services
READ MORE

Off-the-Shelf AAV Products
READ MORE