SMART

This study is a multicenter, randomised, blinded, parallel-group controlled trial conducted among household contacts of index cases of mpox. Households in which one or more individuals have laboratory-confirmed mpox constitute the unit of randomization. Household members receive either the Bavarian Nordic smallpox vaccine as post-exposure prophylaxis or the typhoid vaccine as a control. The co-primary outcomes are RT-PCR–confirmed mpox infection and disease severity.

To assess the primary outcomes, households are randomly assigned to one of two groups: one group receives a single dose of the MVA-Bavarian Nordic smallpox vaccine, and the other group receives a single dose of the Typhim Vi typhoid vaccine. The Typhim Vi vaccine is selected as a control because it provides meaningful protection to individuals living in regions where typhoid fever is endemic. Therefore, participation in either study group may confer a potential benefit to participants.

Baseline data, including a quality-of-life questionnaire, are collected after obtaining informed consent and confirming eligibility. At baseline and each follow-up visit, serum (blood), oropharyngeal swabs, and nasopharyngeal (NP) samples are collected. If a participant presents with lesions, lesion samples are also collected. Quality-of-life assessments are conducted on days 14, 28, and 56. If a participant develops a rash consistent with mpox, a pain assessment questionnaire is also administered.

Following baseline data and sample collection, participants are randomised to receive either (1) the MVA-Bavarian Nordic smallpox vaccine or (2) the Typhim Vi typhoid vaccine. Participants remain blinded to their allocation at the time of vaccination and do not know which vaccine they have received until the end of the trial. Participants or their caregivers are asked to monitor any post-vaccination adverse events by recording information in a standardised diary for 7 days following vaccination. They also complete symptom questionnaires on days 14, 21, and 56 to assess for signs and symptoms of mpox.

In-person visits are conducted on day 7 and day 28. During these visits, participants undergo blood sampling, throat swabs, and NP sampling. If lesions are present, lesion samples are also collected. Throughout the study, if a participant develops signs or symptoms suggestive of mpox, additional samples, including lesion swabs, are collected for laboratory confirmation, following consent.
The final study visit occurs on day 56 post-vaccination. Safety follow-up assessments are conducted at 4 months and 6 months after vaccination.