Evaluating the Human Immune Response to the JYNNEOS Vaccine

Evaluating the Durability of the Human Immune Response to the JYNNEOS Modified Vaccinia Ankara-Bavarian Nordic (MVA-BN) Vaccine

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.

Study Overview

• Status: Not yet recruiting
• Conditions: Virus Diseases; Vaccinia
• Intervention / Treatment: Biological: JYNNEOS (Smallpox and Monkeypox Vaccine, Live, Nonreplicating) suspension for subcutaneous injection; Procedure: Phlebotomy; Procedure: Research bronchoscopy; Procedure: Skin punch biopsy; Procedure: Bone marrow aspiration

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.

• Study Type: Interventional
• Enrollment (Estimated): 20
• Phase: Early Phase 1

Contacts and Locations

• Study Contact: Name: Philip Mudd, MD, PhD; Phone Number: 314-273-1576; Email: pmudd@wustl.edu

Study Locations

• United States
  • Missouri
    • Saint Louis, Missouri, United States, 63110
      • Washington University in Saint Louis School of Medicine Emergency Care and Research Core
      • Contact: Jamie Mills; Phone Number: 314-305-1054; Email: jamiem@wustl.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: Yes

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: MVA-BN vaccinated; MVA-BN vaccine administered: day 0 and day 28 Phlebotomy: within 30 days prior to first vaccine dose, day 0, day 14, day 28, day 35, day 42, day 56, day 90, day 110, day 150, day 210, day 395 Research bronchoscopy: within 30 days prior to first vaccine dose, day 42, day 210, day 395 Skin punch biopsy: within 30 days prior to first vaccine dose, day 42, day 210, day 395 Bone marrow aspiration: within 30 days prior to first vaccine dose, day 56, day 110, day 210, day 395

Biological: JYNNEOS (Smallpox and Monkeypox Vaccine, Live, Nonreplicating) suspension for subcutaneous injection; live, nonreplicating vaccine delivered according to the FDA approved package insert; Procedure: Phlebotomy; Research blood draw; Procedure: Research bronchoscopy; Outpatient research bronchoscopy with bronchoalveolar lavage and endobronchial biopsy performed with conscious sedation.; Procedure: Skin punch biopsy; Skin punch biopsy performed with topical anesthesia.; Procedure: Bone marrow aspiration; Bone marrow aspiration performed with local anesthesia.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Change in magnitude of the MVA-BN antigen-specific T cell response in the blood	Change from day 42 to day 395
Change in magnitude of the MVA-BN antigen-specific antibody response in blood plasma	Change from day 42 to day 395

Secondary Outcome Measures

Outcome Measure	Time Frame
Change in magnitude of the MVA-BN antigen-specific T cell response in the lower airways	Change from day 42 to day 395
Change in magnitude of the MVA-BN antigen-specific antibody response in bronchoalveolar lavage fluid	Change from day 42 to day 395

Other Outcome Measures

Outcome Measure	Time Frame
Evaluate the magnitude and surface phenotype of T cells in the blood, airspace, and skin over time	Through study completion on day 395
Evaluate the magnitude and surface phenotype of B cells in the blood and bone marrow over time.	Through study completion on day 395

Collaborators and Investigators

• Sponsor: Washington University School of Medicine
• Investigators: Principal Investigator: Philip Mudd, MD, PhD, Washington University School of Medicine

Study record dates

Study Major Dates

• Study Start (Estimated): June 1, 2024
• Primary Completion (Estimated): December 1, 2025
• Study Completion (Estimated): December 1, 2025

Study Registration Dates

• First Submitted: April 4, 2024
• First Submitted That Met QC Criteria: April 10, 2024
• First Posted (Actual): April 16, 2024

Study Record Updates

• Last Update Posted (Actual): April 16, 2024
• Last Update Submitted That Met QC Criteria: April 10, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Keywords: T cell; mucosal immunity; neutralizing antibody
• Additional Relevant MeSH Terms: Infections; DNA Virus Infections; Poxviridae Infections; Virus Diseases; Vaccinia; Anti-Infective Agents; Antiviral Agents; Smallpox and monkeypox vaccine modified vaccinia ankara-bavarian nordic
• Other Study ID Numbers: 202312043

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No