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Vaccines
Safe and effective vaccines exist for mpox and additional products are in development
Due to the similarities between variola virus, the cause of smallpox, and MPXV, vaccines developed for smallpox also offer good protection against MPXV.
The mostly commonly used vaccines to date have been MVA-BN and LC16m8 (a live attenuated vaccine). Other vaccines, including mRNA vaccines are in clinical development.
Correlates of protection
The immune response to MPXV is complex, and both antibody-based and cell-mediated immunity is likely to contribute to protection.
A validated correlate of protection would facilitate vaccine design, providing developers with an immune readout to be optimised.
Although neutralising antibody levels are a putative correlate of protection, this has not been formally demonstrated and no protective threshold has been established.
Vaccines knowledge gaps
Primary knowledge gaps identified in the Mpox R&D Roadmap 2026:
Protective immunity
What host responses confer protective immunity and which can be used as correlates of protection?
Optimising protection
How well do existing vaccines protect different populations and what are the requirements for next-generation products?
Population benefits of vaccination
What does real-world evidence reveal about the effectiveness, safety, durability of protection and population-level impact of currently used vaccines?
Outbreak control
What impact do vaccines have on MPXV transmission and outbreak dynamics?
Programme design and implementation
What delivery strategies and programme approaches will maximise mpox vaccination uptake, equity, timeliness and impact in affected communities?
More detailed research questions can be found in the Mpox R&D Roadmap 2026.
Vaccines workplan
Summary of planned CORC activities
Vaccines background
Mpox vaccination is an essential public health intervention, both in historically endemic regions and in non-endemic regions following the expansion of transmission[1]. Currently available mpox vaccines are vaccinia-based orthopoxvirus vaccines targeting smallpox, while newer products designed to improve safety while retaining cross-protection against mpox are in development. These vaccines provide broad protection against orthopoxviruses, including MPXV.
Third-generation live-attenuated vaccinia-based vaccines – MVA-BN (non-replicating in humans) and LC16m8 (minimally replicating in humans) – are the first-line vaccines recommended for preventing mpox[2]. In Africa, 16 countries have received mpox vaccines, and 15 have initiated mpox vaccination for outbreak response since late 2024.
Access remains constrained by high vaccine cost (MVA-BN), limited commercial access (LC16m8), and uneven country readiness linked to policy, regulatory, logistical challenges and other health system priorities. Increasing global supply or the number of approved vaccines may improve availability, but access will continue to depend on affordability, regulatory readiness, delivery capacity, and health system preparedness in endemic countries.
Other licensed smallpox vaccines, such as ACAM2000 (replication-competent live virus) and OrthopoxVac (live-attenuated, minimally replicating), are also approved for mpox as they offer cross-protection against orthopoxviruses in general. Potential issues include their safety in populations such as people living with HIV with immune suppression and pregnant women and children, the feasibility of their administration, and their acceptability to the community. Use of replication-competent vaccinia vaccines must consider the potential for adverse events such as myocarditis/pericarditis, inadvertent inoculation and contact transmission, and the need for associated risk mitigation.
Evidence gaps
Progress has been made recently in mpox vaccine development and vaccination strategies. In particular, the safety profile of MVA-BN is increasingly well established, alternative dosing strategies including intradermal administration are emerging as feasible dose-sparing approaches, and clinical trials are generating data on vaccine use in groups such as pregnant women, adolescents and children.
However, important evidence gaps remain, particularly regarding:
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Durability of protection and booster requirements.
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Vaccine effectiveness in clade I endemic settings.
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Potential for interference following coadministration of other vaccines, particularly childhood vaccines.
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Operational delivery in outbreak and endemic contexts.
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Behavioural and health-system factors that influence acceptability, trust, uptake and equitable access.
These remaining gaps are particularly pronounced in resource-constrained endemic settings, where implementation challenges and health system limitations, constrained laboratory and clinical research capacity, and insufficient implementation and social science research not only affect programme delivery, but also hinder the generation of context-specific evidence needed to strengthen the field and inform vaccination policy and practice[3].
The mpox vaccine development pipeline is reasonably well stocked, with several candidates (mostly mRNA vaccines) in clinical trials and multiple others at advanced stages of pre-clinical development. Clarity is required on the regulatory pathway(s) for new vaccines if traditional phase III efficacy trials are not feasible. These may vary by vaccine platform.
[1] https://www.who.int/publications/i/item/who-wer-9934-429-456
[2] Shafaati M, Forghani S, Shahsavand Davoudi A et al. Current advances and challenges in mpox vaccine development: a global landscape. Ther Adv Vaccines Immunother. 2025;13:25151355251314339. doi: 10.1177/25151355251314339. eCollection 2025.
[3] Furst R, Antonio E, de Swart M, et al. Gaps in the global health research landscape for mpox: an analysis of research activities and existing evidence. BMC medicine 2025; 23(1): 522.
Correlates of protection
Summary of planned COPs-related work