A Clinical Study Investigating the Safety and Immune Responses After Immunization With Investigational Monkeypox Vaccines

Inclusion Criteria (applicable to all substudies unless otherwise specified): * Have given informed consent by signing and dating the informed consent form (ICF) before initiation of any study-specific procedures. * Are willing and able to comply with scheduled visits, treatment schedule, laboratory tests, and other requirements of the study, including the prohibited concomitant medications. This includes that they are able to understand and follow study-related instructions. * SSA and SSD only: Are 18 through 45 years of age (inclusive) at the time of informed consent. * SSB only: Are 50 through 65 years of age (inclusive) at the time of informed consent. * Have a body mass index over 18.5 kg/m\^2 and under 30 kg/m\^2 and weigh at least 50 kg at Visit 0. * Are healthy, in the clinical judgment of the investigator based on volunteer-reported medical history data, physical examination, 12-lead electrocardiogram (ECG), vital signs, and clinical laboratory test results. * SSA and SSD only: Have no prior history of known or suspected smallpox vaccination and no detectable smallpox vaccination characteristic scar (vaccinia-naïve participants). * SSB only: Have a history of prior smallpox vaccination (i.e., are vaccinia-experienced), determined based on medical records and/or presence of smallpox vaccination characteristic scar. The most recent smallpox vaccination should have been received before 1980. * Agree not to enroll in another study with an investigational medicinal product starting from Visit 0 and until the end of this study. * Negative human immunodeficiency virus (HIV)-1 and HIV-2 antigen/antibody blood test result at Visit 0. * Negative Hepatitis B surface antigen and negative core antibodies test results and negative anti Hepatitis C virus antibodies (anti-HCV), or negative Hepatitis C virus (HCV) polymerase chain reaction test result if the anti-HCV is positive at Visit 0. * Volunteers of childbearing potential (VOCBP) must not be pregnant. VOCBP and men who are sexually active with partners of childbearing potential and their sexual partners born female should use a highly effective form of contraception from at least 28 days prior to Dose 1 up to at least 90 days after receiving the last dose of study treatment, and should agree not to donate eggs (ova, oocytes) or sperm. Exclusion Criteria (applicable to all substudies unless otherwise specified): * History of mpox, smallpox or vaccinia infection based on volunteer-reported medical history. * Pregnant, breastfeeding, planning pregnancy or planning to father children starting from Visit 0 and continuously until 90 days after receiving Dose 2. * History of known or suspected severe adverse reaction including allergic reaction (e.g., anaphylaxis) to vaccines or to vaccine components such as lipids. * Current or history of the following medical conditions at Visit 0 or Visit 1: * Uncontrolled, moderate or severe asthma; asthma severity as defined in the US National Asthma Education and Prevention Program Expert Panel report * Chronic obstructive pulmonary disease. * Diabetes mellitus type 1 or type 2, including cases controlled with diet alone (Not excluded: history of isolated gestational diabetes). * Hypertension: If a person has hypertension, exclude for blood pressure that is not well controlled. Well controlled blood pressure is defined as consistently ≤140 mm Hg systolic and ≤90 mm Hg diastolic, with or without medication, with only isolated, brief instances of higher readings, which must be \<150 mm Hg systolic and \<100 mm Hg. * Systolic blood pressure ≥150 mm Hg or diastolic blood pressure ≥100 mm Hg. * Malignancy, excluding localized basal or squamous cell cancer. * Cardiovascular diseases, (e.g., myocarditis, pericarditis, coronary heart disease, myocardial infarction, congestive heart failure, cardiomyopathy or clinically significant arrhythmias, stroke or transient ischemic attack). * Bleeding disorders (e.g., factor deficiency, coagulopathy, or platelet disorder). * Seizure disorder: History of seizure(s) within past 3 years; use of medications in order to prevent or treat seizure(s) at any time within the past 3 years. * Estimated glomerular filtration rate \<60 mL/min/1.73 m\^2. * Chronic liver disease. * Schizophrenia, major depressive disorder, suicidal ideation. Such psychiatric illnesses, as bipolar disorder, autism and attention deficit-hyperactivity disorder that at the discretion of the investigator could interfere with participation and follow-up as outlined by the study. * Current or history of the following diseases associated with immune dysregulation: * Known or suspected immunodeficiency. * History of solid organ or bone marrow transplantation. * Asplenia: any condition resulting in the absence of a functional spleen. * Currently existing or history of any autoimmune disease. * SSA and SSB: At Visit 0, any screening hematology and/or blood chemistry laboratory value that meets the definition of a Grade ≥1 abnormality (according to the FDA toxicity grading scale; see separate exclusion criteria for bilirubin and troponin I). Individuals with any stable Grade 1 abnormalities may be considered eligible at the discretion of the investigator. A stable Grade 1 laboratory abnormality is defined as the value which is ≤ Grade 1 upon repeated testing on a second sample from this individual during the screening period (prior to Visit 1). Individuals with abnormal but not clinically significant parameters not included in the FDA toxicity guidance may be considered eligible at discretion of investigator. * SSD only: At Visit 0, any screening hematology and/or blood chemistry laboratory value (according to the FDA toxicity grading scale) that meets the definition of a Grade ≥2 abnormality; individuals with clinically non-significant Grade 1 abnormalities may be considered eligible at the discretion of the investigator. Individuals with abnormal but clinically non-significant parameters not included in the FDA toxicity guidance may be considered eligible at the discretion of the investigator. See separate exclusion criteria for bilirubin and troponin I. * Abnormal total bilirubin at Visit 0. Note: inclusion of volunteers with bilirubin ≤1.25 upper limit of normal (ULN) if due to Gilbert's syndrome is allowed. * Any abnormal troponin I value at Visit 0. * A 12-lead ECG at Visit 0 which is consistent with probable or possible myocarditis/pericarditis or which demonstrates clinically relevant abnormalities that may affect participant safety or are otherwise clinically significant findings (e.g., complete left bundle branch block, AV block, average corrected QT interval by Fridericia (QTcF interval) \>450 msec, signs of myocardial infarction, ST elevation consistent with myocardial ischemia, or serious brady- or tachyarrhythmias). * Febrile illness (body temperature ≥38.0°C) or other acute illness within 48 hours prior to Dose 1 and/or current (if presented at Visit 1, temporary deferral is allowed). * Participation or planned participation in strenuous or endurance exercise within 7 days before or after each IMP administration. * SSA and SSD only: Vaccination with any Orthopoxvirus-based vaccine including vaccines for prevention of smallpox, disease caused by vaccinia virus or mpox, or vector Orthopoxvirus-based vaccines. * SSB only: Vaccination for prevention of mpox or disease caused by vaccinia virus, or with vector Orthopoxvirus-based vaccine. Vaccination for prevention of smallpox done in or after 1980. * Any vaccination within 28 days before Dose 1. Seasonal inactivated influenza vaccine is allowed, however, it should be administered at least 14 days before IMP administration. * Any non-study IMP within 28 days or five half-lives (whichever is longer) before Dose 1. * Blood/plasma products and/or immunoglobulins within 120 days before Dose 1. * Allergy treatment with antigen injections within 14 days before Dose 1. * Immunosuppressive therapy, including corticosteroids, or radiotherapy within 6 months or five half-lives (whichever is longer) before Dose 1. If systemic corticosteroids have been administered short term (≤14 days, at a dose of ≤20 mg/day of prednisone or equivalent) for treatment of an acute illness, individuals should be enrolled in the study only after corticosteroid therapy has been discontinued for at least 28 days before Dose 1. Intraarticular, intrabursal, or topical (skin or eyes) corticosteroids are permitted. * Have a history of alcohol abuse within 1 year before Visit 0 or have a history of substance abuse within the past 5 years before Visit 0. * Are vulnerable individuals as per ICH E6 definition, i.e., are individuals whose willingness to volunteer in a clinical study may be unduly influenced by the expectation, whether justified or not, of benefits associated with participation, or of a retaliatory response from senior members of a hierarchy in case of refusal to participate.