Phase 1 Trial to Evaluate Safety and Immunogenicity of MVA-BN-EBV in Healthy Young Adults

1. Age ≥18 and ≤30 years at screening
2. Informed consent form (ICF) signed and dated by the participant after reading the form and being advised of the risks and benefits of the trial in a language understood by the participant and before performance of any trial-specific procedures
3. General good health, without any clinically relevant medical illness, physical exam findings, or laboratory abnormalities, as determined by the PI

4. Body mass index (BMI) ≥18.5 and ≤35.0

   • BMI formula for kilograms and meters (round to 1 decimal place): BMI = (body weight in kilograms) / (body height in meters)\^2
   • BMI formula for pounds and inches (round to 1 decimal place): BMI = (body weight in pounds) × 703 / (body height in inches)\^2

5. Assertion by participant that one of the following regarding avoidance of pregnancy is true:

   1. Female participant or female partner(s) of male participant is at least 1 year postmenopausal (amenorrhea >12 consecutive months in the absence of other pathologic or physiologic causes, following cessation of exogenous sex-hormonal treatment, and documented FSH level of ≥40 mIU/mL) at screening
   2. Participant and/or participant's partner(s) is surgically sterile (bilateral oophorectomy, bilateral salpingectomy, hysterectomy, confirmed hysteroscopic sterilization, such as Essure®, vasectomy)
   3. Female participant of childbearing potential or male participant who is sexually active with a female partner of childbearing potential agrees to use a highly effective method of birth control from at least 30 days prior to administration of vaccine until 60 days after last vaccination; medically acceptable methods of contraception that may be used by the participant and/or partner include combined (estrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation (oral, intravaginal, transdermal), progestogen-only hormonal contraception associated with inhibition of ovulation (oral, injectable, implantable), intrauterine device (IUD), intrauterine hormone-releasing system (IUS) , bilateral tubal ligation, or true abstinence (abstinence only acceptable if refraining from heterosexual intercourse during the entire period of 30 days prior to administration of vaccine until 60 days after last vaccination). Periodic abstinence (such as calendar, ovulation, symptothermal, post-ovulation methods) and withdrawal are not acceptable methods of contraception.
   4. Participant is in an exclusively same-sex relationship. These participants should not have plans to become pregnant by any other means for at least 60 days after IMP administration.
6. No plans to become pregnant by intrauterine insemination or in vitro fertilization, to harvest eggs, or to donate or bank sperm through 60 days after last vaccination.
7. Negative HIV antibody test (anti-HIV), negative hepatitis B surface antigen (HBsAG), and negative antibody test to hepatitis C virus (HCV)
8. Willingness to comply with the requirements of the protocol, in the judgment of the investigator

Exclusion Criteria:

1. Pregnancy or breast-feeding
2. Any condition that, in the opinion of the investigator, creates an unacceptable risk to the participant
3. Any condition that, in the opinion of the investigator, will interfere with the conduct of the trial or the validity of the data.
4. Acute or chronic medical condition that, in the opinion of the PI, would render the trial procedures unsafe or would interfere with the evaluation of the responses, including but not limited to, neurologic, cardiovascular, respiratory, hepatic, hematologic, rheumatologic, endocrine, gastrointestinal, renal, autoimmune, or immunosuppressive conditions
5. History of, or active autoimmune disease (vitiligo or thyroid disease requiring thyroid replacement are not exclusions), such as history of Guillain-Barré syndrome or Reye's syndrome
6. Known immunodeficiency syndrome or known or suspected impairment of immunologic functions including, but not limited to, clinically significant liver disease, diabetes mellitus type I, or moderate to severe kidney impairment
7. Known or suspected previous smallpox/mpox vaccination or vaccination with any licensed or investigational poxvirus-based vaccine
8. History of monkeypox, cowpox, or vaccinia infection
9. Close contact with anyone known to have mpox in the 3 weeks prior to signing ICF
10. History of malignancy other than squamous cell or basal cell skin cancer, unless there has been surgical excision at least 6 months prior to screening that is considered to have achieved cure. Participants with history of skin cancer must not be vaccinated at the previous tumor site.
11. Clinically significant mental disorder not adequately controlled by medical treatment
12. Active or recent (within 6 months before screening) evidence of substance abuse (eg, chronic alcohol abuse and/or intravenous and/or nasal drug abuse) that, in the opinion of the investigator, could adversely impact the participant's participation or the conduct of the study
13. History of known or suspected allergic disease or reaction likely to be exacerbated by any component of the vaccine, eg, tris(hydroxymethyl)-amino methane, quail proteins.
14. History of anaphylaxis or severe allergic reaction to any vaccine
15. Receipt of or plans to receive any licensed live vaccine from 30 days prior to first trial vaccination until 30 days after last trial vaccination
16. Receipt of or plans to receive any licensed non live vaccine from 14 days prior to first trial vaccination until 14 days after last trial vaccination
17. Use of any investigational or nonregistered agent within 30 days prior to trial vaccination or plans to receive an investigational agent during the trial until 6 months after last trial vaccination
18. Recent blood donation (including platelets, plasma, and red blood cells) within 4 weeks prior to screening and or planned blood donations through the EAP
19. Use of systemic administration corticosteroids or any other immune modifying drugs defined as use at a dose or equivalent dose of 20 mg of prednisone daily for 14 days or more from 3 months prior to the first trial vaccination to the EAP visit. The use of inhaled, intranasal, topical, ocular, or intraocular steroids is allowed
20. History of organ transplantation, whether or not chronic immunosuppressive therapy is being administered
21. Administration or planned administration of immunoglobulins (with an exception for monoclonal antibodies for treatment of migraines) and/or any blood products from 3 months prior to the first trial vaccination until the EAP visit (packed red blood cells given for an emergency indication in an otherwise healthy person and not required as ongoing treatment is not exclusionary [eg, packed red blood cells given in an emergency during elective surgery])
22. History of coronary heart disease, myocardial infarction, angina, congestive heart failure, cardiomyopathy, stroke or transient ischemic attack, uncontrolled high blood pressure, significant arrhythmia with or without corrective/ablative surgery, abnormal troponin I level > upper limit of normal (ULN), or any other heart condition under the care of a doctor
23. Employment with the PI or CTS, with direct involvement in the proposed study or other studies under the direction of that PI or CTS, or relationship to the PI or CTS employee
24. Relationship with Bavarian Nordic as an employee or employee family member, contractor, agent, or business partner, or having a financial interest in the outcome of the trial