A Phase 2 Randomized Multisite Trial to Inform Public Health Strategies Involving the Use of MVA-BN Vaccine for Mpox

Inclusion Criteria: 1. Individuals 18 - 50 years of age inclusive at the time of consent; OR Adolescent ages 12 to 17 years inclusive at the time of consent. 2. Adult participant is able to read the written informed consent, states willingness to comply with all study procedures and is anticipated to be available for all study visits; OR Parent(s)/Legal Authorized Representative (LAR)(s) of the participating adolescent is able to read and provides written informed permission and participating adolescent provides assent as appropriate for age or development and approved by IRB. Adolescent states willingness to comply with all study procedures and is anticipated to be available for all study visits. 3. . Adult participant is able to understand and agrees to adhere to Lifestyle Considerations during the study; OR Parent(s)/LAR(s) of the participating adolescent is able to understand and states willingness to comply with Lifestyle Considerations. 4. Females of reproductive potential who have sexual intercourse with males must agree to use highly effective contraception for at least 1 month prior to signing ICF and through Day 57. NOTE: See MOP for definitions and list of acceptable and highly effective methods of contraception 5. In good general health as evidenced by medical history, physical examination, and clinical judgement of the investigator to be in stable state of health. NOTE: Participants with pre-existing stable chronic medical conditions defined as conditions not requiring significant change in therapy or hospitalization for worsening disease in the 4 weeks prior to enrollment can be included at the discretion of the investigator. This includes stable, well-controlled HIV positive individuals. 6. Individuals with HIV must be on suppressive ART for at least 6 months, report a CD4 count of greater than 350 cells/µL and no AIDS-defining illness in the last year. Exclusion Criteria: 1. Ever received a licensed or an investigational smallpox or monkeypox vaccine. \*This includes Dryvax, Acam2000, LC 16 m8, MVA-based vaccine candidate or licensed vaccines, and Jynneos, Imvamune or Imvanex) 2. Any history of monkeypox, cowpox, or vaccinia infection. 3. Close contact of anyone known to have monkeypox in the 3 weeks prior to signing ICF 4. Immunocompromised as determined by the investigator 5. Recent or current use of any immunosuppressing medications in the 4 weeks prior to signing ICF. \*\*Topical, ophthalmic, inhaled, intranasal and intraarticular corticosteroids are acceptable, but receipt of \>/=20 mg/day of prednisone or equivalent for \>/=14 consecutive days in the 4 weeks prior to signing ICF is exclusionary. 6. Pregnant or breast feeding. 7. Received or plans to receive a live vaccine or any COVID-19 vaccine in the 4 weeks before or after each study vaccination. 8. Received or plans to receive any other vaccine in the one week before or after each study vaccination. 9. Received experimental therapeutic agent or vaccine in the 3 months prior to signing ICF. 10. Has known allergy or history of anaphylaxis or other serious adverse reaction to a vaccine or vaccine products. \*\*\*This includes individuals with history of severe allergic reaction to gentamicin, ciprofloxacin, chicken or egg protein. 11. Has tattoos, scars, or other marks which would, in the opinion of the investigator, interfere with assessment of the vaccination site. 12. Has any medical disease or condition that, in the opinion of the participating site PI or appropriate sub-investigator, precludes study participation. \*\*\*\*This includes acute, subacute, intermittent, or chronic medical disease or condition that would place the participant at an unacceptable risk of injury, render the participant unable to meet the requirements of the protocol, or may interfere with the evaluation of responses or the participant's successful completion of this trial. 13. Adolescent or adult participant has a history of myocarditis/pericarditis or a history of structural congenital heart defect/cardiac dysrhythmia that, in the opinion of the investigator, poses increased risk to the participant. 14. Adolescent or adult participant has a history of COVID-19 (with positive test for SARS-CoV-2) in the 4 weeks prior to receipt of the first study vaccination. Note: This includes positive rapid antigen test, polymerase chain reaction (PCR) assay, or other nucleic acid amplification (NAAT) test including those performed by the participant at home.