Statement of the WHO Global Advisory Committee on Vaccine Safety (GACVS) on the safety of the mpox vaccines for use in high-risk groups

In July 2022, WHO declared a Public Health Emergency of International Concern (PHEIC) in response to a multi-country outbreak of mpox that was rapidly spreading, mainly through sexual contact, in countries where it had not previously been detected. This PHEIC was lifted in May 2023 following a sustained global decline in cases. The emergence of the new Clade Ib and a resurgence of mpox cases in the African region led to the WHO declaration of a PHEIC again on 14 August 2024. The current outbreak in affected African countries also includes other high-risk groups such as pregnant women and children under the age of 18 years, including infants.

Previously, GACVS reviewed the safety of three available mpox vaccines (MVA-BN, LC16m8, and ACAM2000 vaccines) during the second joint meeting of the WHO GACVS and the WHO Advisory Committee on Safety of Medicinal Products, 14-16 December 2022. The summary of the review and recommendations are published in the Weekly Epidemiological Record (WER)[1]. The "Smallpox and mpox (orthopoxviruses): WHO position paper" published in August 2024, provides guidance for the use of currently available vaccines[2].

On 20 September 2024, the WHO GACVS was updated on safety data from passive and active surveillance from the European Medicines Agency (EMA), US Centers for Disease Control and Prevention (CDC), and Japan Pharmaceuticals and Medical Devices Agency (PMDA) on the two 3rd generation vaccines (modified/non-replicating vaccinia virus (MVA)-BN(Jynneos/Imvanex/Imvamune; Bavarian Nordic) and minimally replicating LC16m8 vaccine (KM-Biologics)). The GACVS was updated on post-approval safety data of MBA-BN vaccines and the safety findings from clinical studies on LC16m8 vaccine.

As MVA-BN is a non-replicating vaccine and can be used in pregnant women, considering limited available data, the GACVS was updated on the risk management plan by Bavarian Nordic for the use of MVA-BN mpox vaccines in African countries. GACVS welcomed additional clinical studies planned by Bavarian Nordic to address questions about vaccine use in infants aged 6 months to 2 years, children aged 2 to 12 years and pregnant women.

While current post-approval data indicate that these vaccines have favorable safety profiles in adults that are generally consistent with pre-licensure clinical trial data, close monitoring is recommended to detect any potential safety signal.

Various administration methods (i.e., subcutaneous, intradermal, and bifurcated needle) are used for different types of mpox vaccines. Therefore, particularly for LC16m8 vaccine, special training of healthcare workers in intradermal injection techniques including the use of a bifurcated needle is strongly recommended to minimize possible immunization error-related adverse events. Local reactogenicity to this vaccine administration will also need to be monitored.

GACVS was briefed on how countries prepare for safety monitoring following vaccine introduction. The Committee was then updated on the draft 'WHO Protocol: Cohort Event Monitoring (CEM) for Active Safety Surveillance of Mpox Vaccines.' GACVS emphasized the importance of using a standardized CEM protocol to capture potential safety signals at an early stage following the introduction of the vaccines, particularly given the limited data for high-risk groups such as infants, children under 12, immunocompromised individuals, and pregnant women.

The Committee emphasizes the importance of monitoring the safety of both mpox vaccines MVA-BN and LC16m8, in all target populations where they are used including its off-label use. It is important to note that while MVA-BN can be used in immunocompromised individuals and pregnant women, LC16m8 is not recommended for use in these populations. Special attention should also be given to infants, children, and lactating women.

The Committee encourages the use of tools like Vigiflow, VigiMobile, and the Med Safety App for spontaneous reporting of adverse events. GACVS recommends that public health authorities, researchers, regulatory agencies, marketing authorization holders, and other key stakeholders conduct comprehensive, coordinated vaccine safety surveillance and studies to identify rare or unknown adverse events not detected during clinical trials in these groups. The 'WHO Protocol: Cohort Event Monitoring for Active Safety Surveillance of Mpox Vaccines' will support countries in implementing cohort event monitoring for mpox vaccines.

It was also noted that there are limitations in applying the restrictions for the use of these vaccines in people living with HIV who have a CD4 cell count below 200 cells/μL due to challenges with access to diagnostics and laboratory testing in these settings. Therefore, the Committee recommended communicating the risks and benefits while closely monitoring and ensuring follow-up on the safety of people living with HIV. Also, there needs to be even more vigilant safety monitoring in vaccinated populations with high HIV prevalence for people who are undiagnosed or not receiving clinical management.

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