Mpox vaccine and emergency use authorization: the role of AVAREF, WHO AFRO in accelerating access in Africa

¹World Health Organization Regional Office for Africa, Cité du Djoue, P.O. Box 06, Brazzaville, Congo

^&Corresponding author
Chioma Stella Ejekam, World Health Organization Regional Office for Africa, Cité du Djoue, P.O. Box 06, Brazzaville, Congo

Commentary    

The ongoing Mpox disease (formerly monkeypox) outbreak in Africa has highlighted the persistent inequities in global vaccine access and the crucial role of regulatory collaboration in responding to public health emergencies [1]. Although the monkeypox virus (MPXV), an orthopoxvirus related to the variola virus, which causes smallpox, had been known for decades and remains endemic in parts of Central and West Africa, causing recurrent sporadic infections and localized outbreaks, vaccination had not previously been part of outbreak control strategies. Smallpox vaccines have long been recognized to provide cross-protection against Mpox. However, following the eradication of smallpox and cessation of routine vaccination in the 1980s, population immunity to orthopoxviruses has declined significantly globally [2].

The 2022 global Mpox outbreak, largely affecting high-income countries in the global north, marked a turning point in the management of the disease and led to the first use of vaccines for outbreak response [3]. Since then, Mpox has evolved from a neglected zoonotic infection in the forested regions of Africa to a multi-country outbreak characterized by sustained human-to-human transmission, including severe cases and fatalities [4].

Several smallpox vaccines have been recommended by the World Health Organization Strategic Advisory Group of Experts on Immunization, including ACAM2000 (a live vaccinia virus vaccine), LC16m8 (an attenuated, replicating smallpox vaccine derived from the lister strain of the vaccinia virus), and MVA-BN (a live attenuated, non-replicating orthopoxvirus derived from the Modified Vaccinia Ankara-Bavarian Nordic strain [5]. The MVA-BN vaccine, a third-generation vaccine, was widely used during the 2022 outbreak, being a non-replicating and safer option, especially for immunocompromised individuals, and is supported by immunogenicity and safety data.

By early 2024, as Mpox cases had surged in the Democratic Republic of Congo (DRC) due to the emergence of clade 1b, they quickly spread to other countries in the region. The exponential growth also highlighted the urgent need to enable timely access to safe and effective vaccines. Rapid deployment of effective vaccines serves as a critical medical countermeasure in outbreak control, interrupting transmission and protecting vulnerable populations at high risk of severe disease [6].

National Regulatory Authorities (NRAs) can use the Emergency Use Authorization (EUA) as a vital mechanism that facilitates the rapid availability of life-saving medical products such as vaccines, therapeutics, and diagnostics during public health emergencies when conventional regulatory approval processes would be too time-consuming [7]. National Regulatory Authorities provide conditional authorizations for the use of unlicensed or unregistered medical products, or approve new indications for already registered ones, based on the best available scientific evidence on quality, safety, and efficacy. This approach typically has conditions, such as the collection of post-authorization safety and effectiveness data, and balances the urgency of emergency response with the need to maintain public health standards. Emergency Use Authorizations are triggered by conditions such as the declaration of the PHEIC by the WHO and/or other events based on the legislation in member states. In Africa, Mpox vaccines were not registered for several reasons, including lack of access, affordability, and the absence of WHO prequalification.

Given the urgency of the outbreak, the AVAREF network coordinated by the WHO Regional Office for Africa (WHO AFRO), played a pivotal role in accelerating vaccine access across the continent. With a mandate to strengthen regulatory capacity and promote coordination among African NRAs and National Ethics Committees (NECs) in Africa, AVAREF facilitates joint reviews of clinical trial applications and supports expedited regulatory pathways such as emergency use authorization. The AVAREF joint reviews mechanism is a collaborative, multi-country process that enables NRAs and NECs from several African countries to conduct a simultaneous, harmonized assessment of the same dossier, whether for clinical trial authorization, emergency use, or product registration. This process aims to streamline decision-making, reduce duplication, and ensure timely and ethically sound oversight of investigational products.

On 14 August 2024, the WHO Director General declared the Mpox outbreak a Public Health Emergency of International Concern (PHEIC) for the second time [8]. Following the PHEIC declaration, the MVA-BN vaccine was granted a WHO Emergency Use Listing (EUL), facilitating procurement, regulatory confidence, and global deployment [9]. By September 2024, MVA-BN was the first Mpox vaccine prequalified, a service that assesses health products to ensure they meet stringent global standards of quality, safety, and efficacy, thereby enhancing its acceptability for procurement by the United Nations and other agencies. This development significantly bolstered vaccine access in low- and middle-income countries, facilitating broader deployment of MVA-BN across Africa and other affected regions [9].

Given that African regulators lean on regulatory reliance and harmonization mechanisms, AVAREF coordinated its joint review to include 14 high-risk African countries (those that had reported cases or where the outbreak was likely to spread at the time of the PHEIC declaration): Benin, Burundi, Cameroon, Central African Republic, Congo, Cote d´Ivoire, Ghana, Liberia, Kenya, Mozambique, Nigeria, Rwanda, South Africa, and Uganda. Together, the countries reviewed MVA-BN dossier, including global safety and effectiveness evidence. The forum issued recommendations endorsing vaccine use across the continent, including guidance on use in countries with robust pharmacovigilance and equitable dose allocation. New high-risk countries have since used the Joint Review Report to facilitate their own EUA processes and grant regulatory approval for the use of the Mpox vaccine. The facilitated review was concluded within 20 working days from the time of initiation. Participating countries received the consolidated technical report of the joint review, which enabled them to make informed scientific decisions within a remarkably short timeframe. Figure 1 details the timeline of the AVAREF facilitated Emergency Authorization of the Mpox Vaccine in Africa from September 2024 to July 2025.

Despite the joint review recommendation, not all participating countries proceeded to grant EUAs on time. This divergence was primarily due to differences in national regulatory procedures, internal clearance processes, and legal frameworks that must be followed at the country level. While the AVAREF joint review significantly reduced the scientific assessment time, several countries did not expedite the EUA process because no Mpox cases had been reported nationally at the time, and no public health emergency had been declared. Furthermore, there is currently no formal agreement obligating countries to automatically adopt AVAREF recommendations, although these are generally considered and appreciated by national authorities. As a result, the time taken by NRAs to issue EUA decisions after the joint review ranged from as few as 5 days to several months.

This highlights the need for a clear and formal decision-making framework to guide national regulatory actions during public health emergencies. Establishing such predefined procedures would reduce delays and enhance operational readiness for future outbreaks. It also calls for alignment of national legislation with reliance principles, the definition of fast-track pathways linked to regional assessments, and the strengthening of institutional capacity to respond rapidly to joint recommendations. The operationalization of the African Medicines Agency (AMA) presents a key opportunity to institutionalize such mechanisms and promote greater convergence and efficiency across the continent.

The declaration of the PHEIC followed the launch of a Joint Continental Incident Management Support Team (IMST), co-led by WHO and Africa CDC [10]. This joint IMST collaborates with Ministries of Health, regional partners, and global stakeholders to expand vaccination efforts, enhance diagnostic access, and strengthen health system resilience. Within this structure, AVAREF leads the Regulatory sub-pillar under the Vaccination pillar, and continues to support member states with available evidence on the Mpox vaccine data and the report of the facilitated multi-country Mpox vaccine joint review report to inform regulatory decisions and facilitate the granting of EUA. As of September 2025, 17 African countries had granted regulatory approval for use of the MVA-BN vaccine for their outbreak response. A significant increase from eight as of October 2024 after the AVAREF joint review.

The Mpox vaccine access experience in Africa illustrates how regional regulatory solidarity, anchored in AVAREF, can transform emergency response and accelerate life-saving interventions even in resource-constrained settings. By enabling EUAs and guiding harmonized adoption across high-risk countries, AVAREF has showcased the power of regulatory reliance and shared expertise. As Africa braces for future outbreaks, embedding such mechanisms into national health security architectures and reinforcing local manufacturing and regulatory capacities will be essential for achieving vaccine equity and epidemic preparedness.

Competing interests     

The authors declare no competing interests.

Authors' contributions     

Chioma Stella Ejekam and Kwasi Nyarko: conceptualization and design of the article; Chioma Stella Ejekam, Rhanda Adechina Adehan, Kwasi Nyarko, and Lynda Rey: first draft of the article; Chioma Stella Ejekam, Rhanda Adechina Adehan, Reena Doshi, Sheillah Nsasiirwe, Ajiri Atagbaza, and Sidy Ndiaye: data acquisition. All the authors have read and approved the final version of this manuscript.

Figure     

Figure 1: timeline of AVAREF facilitated emergency use authorization of Mpox vaccine in Africa 2024-2025

References