This is an open-label, phase 2, immunogenicity and safety trial of the MVA-BN vaccine for the prevention of mpox in adults living with HIV with different level of CD4 counts in Kinshasa, DRC.

The study team aims to investigate whether the administration of 2 standard subcutaneous doses of the Modified Vaccinia Ankara of Bavarian Nordic (MVA-BN) vaccine given 28 days apart, is immunogenic and safe when administered to People Living with HIV (PLHIV) with different levels of CD4 counts in the Democratic Republic of the Congo (DRC).

Enrollment will be stratified according to three different subgroups based on CD4 counts assessed during visit 1A: <200 cells/µL; 200 to 499 cells/µL; ≥ 500 cells/µL. A total of 600 participants will be included in the trial, with 200 participants per subgroup.

All participants will be invited to 6 trial visits over a period of 7 months.

This study will take place in cooperation with the National Programme for the Fight against AIDS (PNLS), the 'Programme Elargi de Vaccination (PEV)' and the 'Institut National de Santé Publique (INSP)'. As part of the response to the current mpox epidemic in DRC, a large cohort of about 10,000 individuals living in Kinshasa will be vaccinated in this program. Vaccination will take place in the Centre Hospitalier Kabinda (CHK) and the Pakadjuma Health Centre. All people living with HIV (PLHIV) with the intention to be vaccinated in the CHK, will be asked for their willingness to participate in the MBOTE-HIVAX clinical trial until the sample size of 600 participants needed for this clinical trial is reached.

Inclusion Criteria:

• Age ≥ 18 years and ≤ 45 years at time of informed consent
• Able and willing to provide written informed consent
• Infected with HIV and receiving combination antiretroviral therapy (ART) for ≥ 8 weeks prior to study entry and vaccination
• Preparedness to follow the study schedule
• Willingness to use contraception for 1 month after each vaccination (only for women of childbearing potential)

Exclusion Criteria:

• A known history of mpox and/or smallpox
• A known history of vaccination with 1st, 2nd or 3rd generation smallpox vaccines, or vaccine platforms that contain MVA as a vector
• Planned MVA-based vaccination (other than study vaccination) during the trial
• Close contact to a confirmed mpox case in the 3 weeks prior to study enrollment
• Uncontrolled severe infection or other condition requiring hospitalization
• Pregnancy
• History of anaphylaxis or severe allergic reaction to any vaccine or known allergy to one of the components of the study vaccine