Extract from report of GACVS meeting of 15-16 May 2025, published in the WHO Weekly Epidemiological Record on 2025

The session on Mpox vaccines focused on reviewing the current status of vaccine safety monitoring in Africa, with a particular emphasis on recent experiences in the Democratic Republic of Congo (DRC), where the majority of Mpox vaccinations have taken place. Kristine Macartney opened the session by stressing the importance of robust safety surveillance systems, effective communication to counter misinformation, and maintaining public trust, all of which are essential for vaccine acceptance and program success.

Mpox remains a significant public health concern in Africa, especially in the DRC, which has received 96% of the over 651,000 doses of the Modified Vaccinia Ankara – Bavarian Nordic (MVABN) vaccine administered on the continent. Another vaccine, LC16, is also available in specific settings. Children aged 1–17 make up nearly 40% of those vaccinated. Although routine pharmacovigilance systems are in place across countries, active follow-up measures like those piloted in Nigeria and Rwanda have proven more effective in capturing adverse events. DRC’s surveillance is limited due to infrastructural and logistical challenges, contributing to a low reporting rate.

Out of 983 adverse events following immunization (AEFIs) reported regionally, 15 were serious. Common reactions include fatigue, fever, and injection site irritation, but reports are often incomplete, and not all serious events are followed up or causally assessed. Disproportionality analysis flagged injection site reactions for further scrutiny, highlighting the need for better administration practices.

A concerning case involving a 25-year-old man with sickle cell disease who died shortly after receiving the MVABN vaccine was presented. Though the timeline suggests a potential link to vaccination, a proper causality assessment is pending due to inadequate hospital cooperation and lack of medical documentation. This underscores the need for improved coordination between hospitals and vaccination programs, especially regarding access to health records. Resistance from some specialized hospitals to release data remains a significant barrier to vaccine safety assessments.

The DRC also launched a Cohort Event Monitoring (CEM) study in Kinshasa to actively track vaccine-related events. With a goal of 30,000 participants, it uses mobile technology to monitor adverse events from day 0 to day 84, focusing on high-risk groups such as children, pregnant individuals, and immunocompromised persons. However, enrollment has been slow, and the long follow-up schedule may challenge participant retention. Adjustments, such as reducing the number of follow-up points and focusing on the critical period within the first two weeks post-vaccination, were recommended to improve feasibility.

Discussion emphasized persistent underreporting in the DRC despite its high vaccination numbers. Nigeria’s integrated pharmacovigilance system and Uganda’s hospital-based committees were noted as effective models to emulate. Social media images of severe injection site reactions also raised concerns about administration quality. These events reinforce the need for improved training and injection safety protocols.

The session concluded with several key recommendations. First, national pharmacovigilance systems must be strengthened by improving training for frontline workers and ensuring full documentation and feedback. Second, active surveillance approaches like CEM should be simplified to enhance follow-up and focus on serious outcomes. Third, vulnerable populations should remain a top monitoring priority. Fourth, misinformation and vaccine hesitancy must be actively countered through tailored communication strategies and collaboration with local leaders. Finally, data sharing must be improved by promoting regular updates to global pharmacovigilance platforms like VigiBase and fostering regional collaboration with countries that have demonstrated effective systems.

Collectively, these strategies aim to build a more resilient, responsive, and trustworthy vaccine safety ecosystem for Mpox in Africa.

Extract from report of GACVS meeting of 12-14 November 2024, published in the WHO Weekly Epidemiological Record on 7 March 2025

Two vaccines are currently available to address the ongoing outbreak of mpox in Africa, which began in 2022. In 2022, the EU approved MVA-BN for mpox prevention in adults (extended in September 2024 to adolescents aged 12–17 years), and the USA granted emergency use authorization for children under 18. In Japan, LC16m8 was licensed in 1975 for smallpox without age restriction, and the indication was extended for the prevention of mpox in August 2022. After the meeting, on 19 November 2024, WHO granted EUL for LC16m8.¹ While MVA-BN can be used in immunocompromised individuals and pregnant women, LC16m8 is not recommended for use in these populations. At an ad hoc meeting in September 2024, GACVS reviewed the safety data on mpox vaccines² and noted that, while current post-market data indicate that these vaccines have favourable safety profiles in adults that are generally consistent with pre-licensure clinical trial data, close monitoring is recommended to detect any potential safety signal.

The Committees were given an update by WHO on mpox vaccine use and safety monitoring in 13 African countries that are currently affected by the outbreak. The African Vaccine Regulatory Forum (AVAREF) facilitated assessment of MVA-BN to enable its emergency use. The AVAREF assessment concluded that, while MVA-BN demonstrates significant potential to address the mpox outbreak, the absence of robust data for certain populations (infants, children, pregnant women and immunocompromised individuals) necessitates ongoing surveillance and booster evaluations. Data on use of mpox vaccines in African populations available at the time of rollout is limited, which indicates that data collection should be integrated with rollout and surveillance systems strengthened. WHO has developed and approved a cohort event monitoring protocol and provided it to countries.³ The primary objectives are to estimate the incidence of serious adverse events in all enrolled vaccinated individuals and to estimate the incidence of local and systemic reactogenicity and other common AEFIs.

GACVS made several recommendations for enhancing the safety surveillance of mpox vaccines; for WHO and other partners to support countries in identifying challenges and bottlenecks in safety surveillance and comprehensively addressing them; to ensure that data collected are of sufficient quality, particularly to capture information on off-label use among key populations with less evidence of safety, including pregnant women, children and immunocompromised individuals; and to ensure that data are presented with coverage data (i.e. rates in exposed populations, especially key populations). Further, countries were encouraged to use the “WHO protocol: cohort event monitoring for active safety surveillance of mpox vaccines” for detection of possible safety signals. Timely data-sharing is necessary to ensure pooling of safety data to facilitate rapid detection of signals, and GACVS recommended that countries expand and enhance use electronic tools to enable faster reporting of AEFIs from the field to national and global levels. Efforts should also be made to strengthen risk communication specific to vaccine safety and to ensure that timely information sharing is provided to  affected communities.

¹ WHO adds LC16m8 mpox vaccine to Emergency Use Listing (https://www.who.int/ news/item/19-11-2024-who-adds-lc16m8-mpox-vaccine-to-emergency-use-listing, accessed January 2025).

²Statement of the WHO Global Advisory Committee on Vaccine Safety (GACVS) on the safety of the mpox vaccines for use in high-risk groups (https://www.who.int/ news/item/04-10-2024-statement-gacvs-safety-mpox-vaccines-for-use-in-highrisk-groups, accessed January 2025).

³Safety monitoring of mpox vaccines using cohort event monitoring a WHO protocol. Geneva: World Health Organization; 2024 (https://iris.who.int/handle/10665/379659, accessed January 2025). License: IGO CC BY-NG-SA 3.0.

Extract from the second joint meeting of WHO GACVS and WHO ACSoMP, published in the WHO Weekly Epidemiological Record of 3 March 2023

Mpox, previously called monkeypox, is an infectious disease endemic to central and west Africa caused by the double-stranded DNA mpox virus. The virus is a member of the Orthopoxvirus genus in the Poxviridae family, related to the virus which caused smallpox which was eradicated in 1980. On 23 July 2022, WHO declared the global mpox outbreak to be a public health emergency of international concern (PHEIC) following reports of mpox outbreaks in multiple non-endemic countries. The number of reported cases peaked in August 2022 and has since declined. In early August 2022, the highest numbers of cases were confirmed in Europe and USA and there was an ongoing outbreak in several African countries.

Currently, three vaccines are available, one second generation (ACAM2000 (Emergent Biosolutions)) and two third generation vaccines (modified vaccinia virus (MVA)-BN (Jynneos/Imvanex/Imvamune; Bavarian Nordic) and Lc16m8 (KM-Biologics)). WHO interim guidance published in November 2022 contains information on mpox vaccine safety).[1]

GACVS discussed mpox vaccine-associated adverse events following immunization (AEFI)s and serious AEFI reporting and investigation, active surveillance for adverse events of special interest (AESIs), mpox vaccine safety communication, data collection tools, historical AEFI data for smallpox vaccines and case definitions for serious AEFIs.

The safety profile of ACAM2000 includes risks for myocarditis and pericarditis and many of the risks associated with replication-competent smallpox vaccines. The safety of the third-generation vaccine, MVA-BN, has been assessed in 22 clinical trials that included over 7800 participants aged ≥18 years. Similar rates of adverse events (AEs) in vaccinia-naïve and previously vaccinated individuals were observed. The safety of this vaccine has been assessed in special populations (e.g., HIV, atopic dermatitis, children, pregnant and breastfeeding women) with no safety concerns identified, however, the size of the study samplea were small. The safety assessment of intradermal administration of the MVA-BN vaccine showed an increased rate of local reactogenicity reactions. The second third-generation vaccine, Lc16m8, has been used mainly in Japan, and two recent studies in Japan and USA reported no safety concerns.

The post marketing data available for MVA-BN show no safety concerns but there are gaps in knowledge on safety and benefit-risk and more data are needed for specific populations, such as children, pregnant women, populations outside of USA, Europe and Australia, immunocompromised populations and those previously vaccinated.

In conclusion in 2022, after more than 1 million MVA-BN doses having been used, the safety profile, predominantly assessed in adult males, is good, both for subcutaneous and intradermal administration and consistent with the safety profile reported in clinical trials. Although the rates of local adverse events with intradermal administration were higher than with subcutaneous administration, none were serious. No safety signal has been observed for excess risk of myocarditis or pericarditis.