Two mRNA vaccines are nearing the end of Phase I/II trials, poised to potentially reshape pivotal study designs for mpox prevention. Simultaneously, investigations are underway to explore vaccine options for pediatric populations, addressing a critical gap in protection.
mRNA Vaccine Candidates in Clinical Trials
Moderna is currently conducting a Phase I/II trial (NCT05995275) to evaluate the safety, tolerability, and immunogenicity of its mRNA mpox vaccine, mRNA-1769, in healthy adult participants. This trial, spanning multiple sites across the UK, is slated to conclude in June 2025. According to Anaelle Tannen, an infectious disease analyst at GlobalData, the trial design should reveal the true benefits of the vaccine candidate, acknowledging that the sponsor’s knowledge of these kinds of drugs will have helped while they were designing the study. "The use of mRNA technology will likely become more widespread, with trials occurring across various other disease indications. Whilst interim results are yet to be published, the design of the trial, as an RCT is good. Furthermore, the trial is occurring over 22 months and involves 351 participants across 12 sites which increases the power and validity of the study,” says Tannen.
Echoing this sentiment, Dr. David Schwartz, a medical epidemiologist and board-certified pathologist, expressed high hopes for Moderna’s candidate, citing promising preclinical data. "Moderna’s mRNA proved to be a very effective product in the preclinical study. All subjects in the investigative arm survived compared to non-immunised controls and these subjects also had fewer mpox lesions...they’re incredibly safe overall," Schwartz noted.
BioNTech SE is also in the race with its mRNA vaccine candidate, BNT-166A. Their Phase I/II trial (NCT05988203) is designed to assess the safety, tolerability, reactogenicity, and immunogenicity of BNT166a for active immunization against mpox in adults aged 18 to 65. The study, conducted across sites in the US and UK, is expected to be completed by May 2025. "BioNTech also has experience with mRNA technology and has marketed several Covid-19 mRNA vaccines. The trial is taking place over a shorter period, only 12 months, compared to Moderna’s drug candidate, and includes only 64 participants across nine sites. While this study design is sufficient, the Moderna trial is definitely stronger,” Tannen added.
Dr. Itzchak Levy, director of the HIV/AIDS center and expert in infectious diseases at Israel’s Sheba Hospital, conveyed optimism for both mRNA candidates, stating, "Of course, the first great success was in Covid-19 so I think that it’s so obvious that it will also be quite effective in mpox...I think that it’s important to develop more vaccines and I believe these will be mRNA."
Jynneos Investigated for Pediatric Use
Bavarian Nordic's Jynneos vaccine, already approved for mpox and smallpox prevention in adults, is now under investigation for pediatric use in the Democratic Republic of Congo. The Phase II trial (NCT06549530) involves 460 patients and aims to evaluate the immunogenicity and safety of Jynneos in children aged two to less than 12 years, compared to adults aged 18-50 years. The trial is scheduled for completion in June 2025.
Tannen and Schwartz both expressed optimism about the trial, mostly because it is targeting key populations who are currently more at risk of contracting the virus, which neither Moderna’s or BioNTech’s candidates are yet targeting. "What we’ve seen with a mpox during this particular outbreak is that it tends to be infecting younger people and so children are especially at risk. I think that study will therefore provide valuable information, and we also need studies on pregnant women," says Schwartz.
"The trial is planned to occur over seven months in the Democratic Republic of Congo, where the current outbreak is. There is a great need for more vaccines as well as vaccines that are effective across all age groups as the outbreak continues to grow,” says Tannen.
Levy is happy to see a trial involving paediatric patients but has some concerns about this vaccine. "Current vaccines are still using the active virus which can trigger adverse events, especially in patient populations who are immunocompromised. This will not be as prevalent with mRNA because it is proteins rather than the active virus," adds Levy.
