Clinical trial NCT06366672: Evaluating the Human Immune Response to the JYNNEOS Vaccine
Official title: Evaluating the Durability of the Human Immune Response to the JYNNEOS Modified Vaccinia Ankara-Bavarian Nordic (MVA-BN) Vaccine
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: EARLY_PHASE1
Conditions: Vaccinia
Virus Diseases
Keywords: T cell
neutralizing antibody
mucosal immunity
Lead sponsor: Washington University School of Medicine
Sponsor class: OTHER
First posted: 2024-04-16
Enrollment: 20
Sex: ALL
Minimum age (years): 18
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: Participants will be vaccinated with MVA-BN according to the FDA-approved labeling and immune responses in the blood, lung mucosa, skin, and bone marrow will be monitored prior to and following vaccination using phlebotomy, research bronchoscopy, skin punch biopsy, and bone marrow aspiration procedures.
Primary purpose: BASIC_SCIENCE

Brief summary: 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.

Detailed description: 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.

Eligibility criteria: 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

Primary outcomes:
measure: Change in magnitude of the MVA-BN antigen-specific T cell response in the blood
timeFrame: Change from day 42 to day 395
measure: Change in magnitude of the MVA-BN antigen-specific antibody response in blood plasma
timeFrame: Change from day 42 to day 395
Secondary outcomes:
measure: Change in magnitude of the MVA-BN antigen-specific T cell response in the lower airways
timeFrame: Change from day 42 to day 395
measure: Change in magnitude of the MVA-BN antigen-specific antibody response in bronchoalveolar lavage fluid
timeFrame: Change from day 42 to day 395
Other outcomes:
measure: Evaluate the magnitude and surface phenotype of T cells in the blood, airspace, and skin over time
timeFrame: Through study completion on day 395
measure: Evaluate the magnitude and surface phenotype of B cells in the blood and bone marrow over time.
timeFrame: Through study completion on day 395
Locations:
city: Saint Louis
country: United States
facility: Washington University in Saint Louis School of Medicine Emergency Care and Research Core
state: Missouri
Study officials:
affiliation: Washington University School of Medicine
name: Philip Mudd, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: