This study is designed to evaluate the magnitude and duration of the human adaptive immune response to the JYNNEOS Modified Vaccinia Ankara-Bavarian Nordic (MVA-BN) vaccine in the blood, lung mucosa, skin and bone marrow.

Orthopoxvirus vaccination leads to very high magnitude antigen-specific T cell responses and neutralizing antibody responses that can be detected in blood decades after vaccination. Despite a large number of previous studies of human immune responses to Modified Vaccinia Ankara (MVA) vaccination in blood, very few of these previous studies evaluate the human mucosal immune response to MVA in the lung and skin, or the immune response to MVA vaccination in the bone marrow. The development of methods to explore human immune responses in these key immunologic compartments now allows the evaluation of the induction of immune responses in these human tissues using the MVA vaccine system.

Inclusion Criteria:

• 18-60 year old otherwise healthy participants

Exclusion Criteria:

• Prisoners
• Participants unable to provide full written informed consent
• Previous receipt of a smallpox or monkeypox vaccine
• Previous infection with monkeypox
• Receipt of any vaccine in the 28 days prior to the first study procedure or planned receipt of any vaccine outside of those provided in the current study before completion of the study day 42 visit.
• Immunocompromise (primary or secondary due to other medical conditions or medications)
• Previous organ transplant
• Active malignancy
• Pregnancy
• < 4 weeks post-partum or actively breastfeeding
• Female participants who are not actively on hormonal contraception or do not have an intrauterine device in place
• Body Mass Index > 40
• Current smokers
• History of a known chronic pulmonary, cardiovascular, renal, hepatic, hematologic or metabolic disorder. Participants with isolated treated hypertension as the only cardiovascular disorder may be included in the study.
• History of a chronic neurologic or neurodevelopmental condition. This does not exclude potential participants with chronic back pain or previous disk herniation/back surgery, only participants with documented weakness, quadriplegia or paraplegia. This exclusion criterion also does not exclude from the study participants with recurrent migraine headaches as the only chronic neurologic condition.
• Pulse oxygen saturation value of 92% or less on room air at study enrollment or on the day of bronchoscopy
• Any significant infiltrate or pleural effusion on upright posterior-anterior and lateral chest x-ray imaging performed on the day of bronchoscopy
• International Normalized Ratio value greater than 1.4 or a Partial Thromboplastin Time value of greater than 40 seconds at study enrollment
• Platelet count of less than 100,000 at study enrollment