Mpox Booster Trial

The Public Health Agency of Sweden leads a three-year clinical trial that evaluates safety and immune responses to a booster dose of the MVA-BN mpox vaccine. Researchers in four countries are studying if it is safe to administer a booster dose and how long the immune response lasts, how well the booster works when given by different routes, and how immune responses differ between individuals with different medical background, including HIV- and non-HIV infected.

The trial includes 640 participants and is coordinated with academic and public health partners in Belgium, France, Ireland and Sweden.

Why the study matters

Mpox continues to cause outbreaks in Europe and globally. Many people received a primary mpox vaccination in recent years, but we still lack clear knowledge of how strong and long-lasting their protection is. Clusters of breakthrough infections have occurred.

This study helps answer key questions:

• Does a booster dose strengthen immune responses?
• Is it safe to give a booster dose?
• Is intradermal (ID) immunisation as effective as subcutaneous (SC)?
• Does a mucosal immune response develop following a primary immunisation and is it strengthened by a booster dose?
• How do immune responses differ between individuals and over time?
• Can new mpox vaccines be evaluated quickly if they become available?

Who is involved

The trial brings together national public health authorities, academic institutions and clinical networks:

• Public Health Agency of Sweden (PHAS): Sponsor and overall coordinator for the trial as well as coordinating the largest trial site and hosting the laboratory assessing mpox-specific binding and neutralizing antibodies.
• Karolinska Institutet (KI): Hosts the clinical database, manages data and statistical analyses.
• Assistance Publique – Hôpitaux de Paris (AP-HP): Engages clinical sites in France as well as three different laboratories assessing mpox-specific B-memory and T-cells as well as vacciniavirus-specific neutralizing antibodies.
• Institute of Tropical Medicine (ITM), Belgium: Engages clinical site at ITM.
• University College Dublin (UCD): Engages clinical sites in Ireland and is laboratory partner assessing in depth neutralizing cross-immunity against different mpox virus clades and through O-link assays.

Clinical sites across the four countries will recruit participants and collect clinical and laboratory samples.

How the trial is governed

Steering Committee

The Steering Committee meets weekly and includes representatives from all partner countries. It oversees trial progress, coordination and scientific decisions.

Data Safety Monitoring Board

A board of independent experts reviews safety data throughout the trial.

Scientific Advisory Board

Scientific experts from public health agencies, academic institutions and the communities at risk provide advice on methodology, safety, scientific quality and scientific interpretation.

Specifically, representatives from the WHO Strategic Advisory Group of Experts on immunisations (WHO SAGE), Africa Centres for Disease Control and Prevention (Africa CDC) and the patient organisation POSITHIVA GRUPPEN participate in the SAB to ensure timely transfer of acquired scientific knowledge to those that can implement results obtained.

What the study measures

The study follows a registered and approved protocol in the EU Clinical Trial Information System (CTIS). The scientific proceedings of the study can be followed here:

Study on the Safety and Immune Response of the MVA-BN Vaccine Booster for Monkeypox Prevention in Previously Vaccinated Patients (clinicaltrials.eu).

Primary objective

• Compare immune response at baseline with Month 1 after an MVA-BN booster dose given intradermally versus subcutaneously.

Secondary objectives include

• Immune response at Month 6
• Durability of antibodies over time up to 24 months
• Detailed assessments of B-cell, T-cell and mucosal immunity in a subset of participants
• Safety and adverse events
• Breakthrough infections during the 24-month follow-up

Possible future objective

If a new mpox vaccine becomes available, the EU CTIS-approved adaptive design allows evaluation of a new booster arm through a future protocol amendment.

How the trial works

Participants attend 6–7 visits over three years. At each visit, staff collect clinical information and biological samples, including:

• blood samples,
• optional cellular immunology samples in substudy groups,
• optional mucosal immunology in oral and rectal samples.

A digital 7-day safety diary captures short-term reactions after vaccination and long-term safety will be monitored through routine visits.

Data management

Karolinska Institutet hosts the secure REDCap database used for all clinical data. Laboratory results are transferred securely and linked through pseudonymised participant IDs.

Trial timeline

• 2025 (Q3): 3-year contract signed with European Health and Digital Executive Agency (HaDEA) implementing EU funding programmes
• 2025 (Q4): Recruitment started
• 2026 (Q2): Recruitment expected to be finalised
• 2026 (Q3): Primary outcome analysis and results (Month 1 post-booster)
• 2026–2028: Long-term clinical follow-up and laboratory analyses
• 2028 (Q3): Final data analysis and reporting