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Immunology of Ebola Vaccine

Primary Purpose

Ebola Virus Disease

Status
Not yet recruiting
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Recombinant Vesicular Stomatitis Vaccine for Ebola (rVSV∆G-ZEBOV-GP)
Sponsored by
Emory University
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional basic science trial for Ebola Virus Disease focused on measuring vaccine, vaccination, immune response

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesAccepts Healthy Volunteers

Inclusion Criteria: Signed informed consent for study. For women of childbearing potential: willing to engage in effective methods of contraception starting at least 28 days prior to vaccination and during the study. Willing to minimize blood and body fluid exposure to others (encourage abstinence, and hand hygiene; discourage contact with blood, vomit, feces without personal protective equipment (PPE) for at least 14 days following vaccine administration. Willing to forgo blood donation until 56 days following vaccination. Exclusion Criteria: At risk of travel-related or occupational exposure to Ebola virus such as through laboratory, clinical contact, field work, or in the judgment of the investigator. Received any Ebola vaccines or have history of Ebola Virus Disease (EVD). Current or previous diagnosis of immunocompromising condition such as human immunodeficiency virus or other immunosuppressive condition by receiving systemic immunosuppressants or immune-modifying drugs for >14 days in total within 6 months prior to screening (for corticosteroids: ≥ 10mg/day of prednisone or equivalent) or anticipates the need for immunosuppressive treatment at any time during participation in the study. Pregnant and/or breastfeeding (must have urine pregnancy test on the day of vaccination and during screening visit) Known allergy to any component of the rVSV∆G-ZEBOV-GP vaccine products (VSV, albumin, tris). History of severe local or systemic reactions to any vaccination. Received investigational drug within 5 half-lives or 28 days, whichever is longer, prior to study vaccination. Received or intends to receive vaccines within 28 days prior to or following study vaccination. Received immunoglobulins and/or any blood products within 120 days prior to study vaccination. Clinical evidence of systemic infection or other acute intercurrent illness (e.g. oral temp >38°C or > 100.4°F) less than 72 hours prior to study vaccination. Currently has symptomatic, acute, or unstable chronic disease requiring medical or surgical care, to include significant change in therapy or hospitalization, at the discretion of the investigator. History of excessive alcohol consumption, drug abuse, psychiatric conditions, social conditions, or occupational conditions that in the opinion of the investigator would preclude compliance with the study. Any condition that would limit the ability of the participant to meet protocol requirements or would place the participant at unreasonable risk in the opinion of the investigator.

Sites / Locations

  • The Hope Clinic of the Emory Vaccine Center

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Recombinant Vesicular Stomatitis Vaccine for Ebola (rVSV∆G-ZEBOV-GP)

Arm Description

Healthy adults who are at no risk for exposure to Ebola Virus and are not prior recipients of an Ebola vaccine receive a single dose of recombinant Vesicular Stomatitis Vaccine for Ebola (rVSV∆G-ZEBOV-GP).

Outcomes

Primary Outcome Measures

Ebola-specific antibodies
Ebola-specific antibodies following rVSV∆G-ZEBOV-GP vaccination will be measured.

Secondary Outcome Measures

Frequency of Adverse Events (AEs)
The safety profile of rVSV∆G-ZEBOV-GP vaccination is assessed as the frequency of adverse events. Solicited injection site reactions and systemic symptoms will be assessed using a diary over the 14 days following vaccination. Unsolicited adverse events will be collected over 28 days following vaccination.
Severity of Adverse Events
The safety profile of rVSV∆G-ZEBOV-GP vaccination is assessed as the severity of adverse events. Solicited injection site reactions and systemic symptoms will be assessed using a diary over the 14 days following vaccination. Unsolicited adverse events will be collected over 28 days following vaccination. The severity of adverse events is graded according to the criteria set forth in the National Cancer Institute's Common Terminology Criteria for Adverse Events (NCI-CTCAE) manual. All adverse events are graded on a scale from 1 to 5 according to the standards in the NCI-CTCAE manual, where Grade 1 is mild, Grade 2 is moderate, Grade 3 is severe or medically significant but not immediately life-threatening, Grade 4 is life-threatening consequences, and Grade 5 is death related to the adverse event.
Frequency of Serious Adverse Events
The safety profile of rVSV∆G-ZEBOV-GP vaccination is assessed as the frequency of serious adverse events. A serious adverse event is an adverse event resulting in one more of the following consequences: death, a life-threatening event, an inpatient hospitalization or prolongation of an existing hospitalization, a persistent or significant incapacity or substantial disruption of the ability to conduct normal life functions, or a congenital anomaly/birth defect.
Frequency of Adverse Events Related to Fine Needle Aspiration/Biopsy of Lymph Node
The safety profile of fine needle aspirate and core biopsy of lymph nodes is assessed as the frequency of adverse events related to the fine needle aspiration or biopsy of the lymph node procedure.
Severity of Adverse Events Related to Fine Needle Aspiration/Biopsy of Lymph Node
The safety profile of fine needle aspirate and core biopsy of lymph nodes is assessed as the severity of adverse events related to the fine needle aspiration or biopsy of the lymph node procedure. The severity of adverse events is graded according to the criteria set forth in the National Cancer Institute's Common Terminology Criteria for Adverse Events (NCI-CTCAE) manual. All adverse events are graded on a scale from 1 to 5 according to the standards in the NCI-CTCAE manual, where Grade 1 is mild, Grade 2 is moderate, Grade 3 is severe or medically significant but not immediately life-threatening, Grade 4 is life-threatening consequences, and Grade 5 is death related to the adverse event.
Frequency of Adverse Events Related to Bone Marrow Aspiration
The safety profile of bone marrow aspirates is assessed as the frequency of adverse events related to the bone marrow aspiration procedure.
Severity of Adverse Events Related to Bone Marrow Aspiration
The safety profile of bone marrow aspirates is assessed as the severity of adverse events related to the bone marrow aspiration procedure. The severity of adverse events is graded according to the criteria set forth in the National Cancer Institute's Common Terminology Criteria for Adverse Events (NCI-CTCAE) manual. All adverse events are graded on a scale from 1 to 5 according to the standards in the NCI-CTCAE manual, where Grade 1 is mild, Grade 2 is moderate, Grade 3 is severe or medically significant but not immediately life-threatening, Grade 4 is life-threatening consequences, and Grade 5 is death related to the adverse event.

Full Information

First Posted
October 20, 2023
Last Updated
October 20, 2023
Sponsor
Emory University
Collaborators
Washington University School of Medicine, Merck Sharp & Dohme LLC
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1. Study Identification

Unique Protocol Identification Number
NCT06100913
Brief Title
Immunology of Ebola Vaccine
Official Title
An Open-label Interventional Study to Understand and Quantify the Duration of Humoral Immunological Memory to a Single Dose of Recombinant Vesicular Stomatitis Vaccine for Ebola (rVSV∆G-ZEBOV-GP)
Study Type
Interventional

2. Study Status

Record Verification Date
October 2023
Overall Recruitment Status
Not yet recruiting
Study Start Date
November 2023 (Anticipated)
Primary Completion Date
December 31, 2026 (Anticipated)
Study Completion Date
December 31, 2026 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Emory University
Collaborators
Washington University School of Medicine, Merck Sharp & Dohme LLC

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

Brief Summary
In this study 30 healthy adult participants will receive a single dose of an Ebola vaccine. Blood samples, fine needle aspirates, core biopsies, and bone marrow aspirates will be collected prior to and following vaccination to assess immune responses in the blood, lymph nodes, and bone marrow over multiple time points.
Detailed Description
Ebolaviruses (EBOV), cause Ebola Virus Disease, a condition characterized primarily by hemorrhagic fevers with remarkably elevated mortality rates. The genus Ebolavirus encompasses five distinct viral species, namely Bundibugyo virus (BDBV), Zaire Ebola virus (ZEBOV), Reston virus (RESTV), Sudan virus (SUDV), and Taï Forest virus (TAFV). More than 20 human outbreaks have been reported world-wide since the identification of EBOV in the late 1970s. The most common geographical region affected by EBOV outbreaks is Central Africa, with two of the most notable outbreaks occurring in Kikwit, Democratic Republic of Congo in 1995, and Gulu, Uganda in 2000. Outside of Africa, EBOV infections have been reported in countries like Philippines, Italy, United Kingdom, United States of America, and others. Of particular significance is the 2014-2016 West African ZEBOV outbreak, which is known as the most extensively recorded outbreak to date with over 28,000 reported infections and a 40% approximated mortality rate. The outbreak significantly surpassed all preceding ZEBOV outbreaks in terms of geographical coverage, number of impacted individuals, and its disruptive influence on conventional societal activities. Fatal ZEBOV infection is characterized by flu-like symptoms and high fever followed by multi-organ failure. While case-fatality rates vary between outbreaks and among the Ebola viruses, ZEBOV has been associated with up to 90% lethality. While specific treatment strategies including convalescent plasma, monoclonal antibodies, and/or direct- acting antiviral agents are being pursued, it is unlikely that treatment directed at the individual will be sufficient to control outbreaks. Hence, it is important to investigate prophylactic vaccines that confer protection against Ebola viruses in at-risk populations to prevent future outbreaks. Understanding the durability of these vaccines is of paramount importance. The recombinant vesicular stomatitis virus-based Ebola vaccine (rVSVΔG-ZEBOV-GP) was approved in 2019 as a single dose in the prevention against Ebola virus disease (EVD). Protection is primarily conferred by antibodies targeting the ZEBOV glycoprotein (GP), and ZEBOV-GP Immunoglobulin G (IgG) memory B cells (MBCs) can be detected in the blood 6 months following vaccination. It is not fully understood, however, whether a single dose of rVSVΔG-ZEBOV-GP effectively generates germinal center (GC) responses that result in durable immunological memory. The immune responses that ensue following vaccination consist of a series of highly orchestrated events in GCs of secondary lymphoid organs. The nature of these interactions ultimately dictates the quality and longevity of the immune response generated following vaccination. Long-lived bone marrow plasma cells (BMPCs) and MBCs are the end products of the GC reaction. Previous studies of human B cell immune responses to rVSVΔG-ZEBOV-GP vaccination have focused on the blood compartment. This strategy ignores the critical compartments of draining lymph nodes (dLNs), where GCs are formed, and bone marrow, the major reservoir of BMPCs. This study aims to directly examine the GC response induced in the dLNs after vaccination with rVSVΔG- ZEBOV-GP. The researchers will directly probe ZEBOV-GP-specific GC B cell responses and determine how long these GCs persist after a single vaccine dose. The researchers will determine the frequency of antigen-specific BMPCs that home to bone marrow after vaccination, and whether these BMPCs persist up to 1 year after a single dose. The researchers will determine the frequency of antigen-specific MBCs generated after vaccination. Across all compartments, we will analyze the B cell receptor (BCR) clonal diversity and the degree of somatic hypermutation (SHM) induced by vaccination. This study will determine the degree to which a single dose of rVSVΔG-ZEBOV-GP generates durable GC responses and long lasting humoral immunological memory.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Ebola Virus Disease
Keywords
vaccine, vaccination, immune response

7. Study Design

Primary Purpose
Basic Science
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
30 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Recombinant Vesicular Stomatitis Vaccine for Ebola (rVSV∆G-ZEBOV-GP)
Arm Type
Experimental
Arm Description
Healthy adults who are at no risk for exposure to Ebola Virus and are not prior recipients of an Ebola vaccine receive a single dose of recombinant Vesicular Stomatitis Vaccine for Ebola (rVSV∆G-ZEBOV-GP).
Intervention Type
Biological
Intervention Name(s)
Recombinant Vesicular Stomatitis Vaccine for Ebola (rVSV∆G-ZEBOV-GP)
Other Intervention Name(s)
Ervebo
Intervention Description
The study vaccine is an FDA-approved recombinant vesicular stomatitis virus (rVSV) expressing the envelope glycoprotein of Ebola virus Zaire (rVSV∆G-ZEBOV-GP). The dose of rVSV∆G-ZEBOV-GP vaccine has been chosen for this study as per package insert recommendations and based on clinical data. Participants receive 1.0 milliliter (mL) of the study vaccine administered intramuscularly in the deltoid muscle of the non-dominant arm.
Primary Outcome Measure Information:
Title
Ebola-specific antibodies
Description
Ebola-specific antibodies following rVSV∆G-ZEBOV-GP vaccination will be measured.
Time Frame
Day 29, Day 366
Secondary Outcome Measure Information:
Title
Frequency of Adverse Events (AEs)
Description
The safety profile of rVSV∆G-ZEBOV-GP vaccination is assessed as the frequency of adverse events. Solicited injection site reactions and systemic symptoms will be assessed using a diary over the 14 days following vaccination. Unsolicited adverse events will be collected over 28 days following vaccination.
Time Frame
Up to Day 28
Title
Severity of Adverse Events
Description
The safety profile of rVSV∆G-ZEBOV-GP vaccination is assessed as the severity of adverse events. Solicited injection site reactions and systemic symptoms will be assessed using a diary over the 14 days following vaccination. Unsolicited adverse events will be collected over 28 days following vaccination. The severity of adverse events is graded according to the criteria set forth in the National Cancer Institute's Common Terminology Criteria for Adverse Events (NCI-CTCAE) manual. All adverse events are graded on a scale from 1 to 5 according to the standards in the NCI-CTCAE manual, where Grade 1 is mild, Grade 2 is moderate, Grade 3 is severe or medically significant but not immediately life-threatening, Grade 4 is life-threatening consequences, and Grade 5 is death related to the adverse event.
Time Frame
Up to Day 28
Title
Frequency of Serious Adverse Events
Description
The safety profile of rVSV∆G-ZEBOV-GP vaccination is assessed as the frequency of serious adverse events. A serious adverse event is an adverse event resulting in one more of the following consequences: death, a life-threatening event, an inpatient hospitalization or prolongation of an existing hospitalization, a persistent or significant incapacity or substantial disruption of the ability to conduct normal life functions, or a congenital anomaly/birth defect.
Time Frame
Up to Day 366
Title
Frequency of Adverse Events Related to Fine Needle Aspiration/Biopsy of Lymph Node
Description
The safety profile of fine needle aspirate and core biopsy of lymph nodes is assessed as the frequency of adverse events related to the fine needle aspiration or biopsy of the lymph node procedure.
Time Frame
Up to Day 366
Title
Severity of Adverse Events Related to Fine Needle Aspiration/Biopsy of Lymph Node
Description
The safety profile of fine needle aspirate and core biopsy of lymph nodes is assessed as the severity of adverse events related to the fine needle aspiration or biopsy of the lymph node procedure. The severity of adverse events is graded according to the criteria set forth in the National Cancer Institute's Common Terminology Criteria for Adverse Events (NCI-CTCAE) manual. All adverse events are graded on a scale from 1 to 5 according to the standards in the NCI-CTCAE manual, where Grade 1 is mild, Grade 2 is moderate, Grade 3 is severe or medically significant but not immediately life-threatening, Grade 4 is life-threatening consequences, and Grade 5 is death related to the adverse event.
Time Frame
Up to Day 366
Title
Frequency of Adverse Events Related to Bone Marrow Aspiration
Description
The safety profile of bone marrow aspirates is assessed as the frequency of adverse events related to the bone marrow aspiration procedure.
Time Frame
Up to Day 366
Title
Severity of Adverse Events Related to Bone Marrow Aspiration
Description
The safety profile of bone marrow aspirates is assessed as the severity of adverse events related to the bone marrow aspiration procedure. The severity of adverse events is graded according to the criteria set forth in the National Cancer Institute's Common Terminology Criteria for Adverse Events (NCI-CTCAE) manual. All adverse events are graded on a scale from 1 to 5 according to the standards in the NCI-CTCAE manual, where Grade 1 is mild, Grade 2 is moderate, Grade 3 is severe or medically significant but not immediately life-threatening, Grade 4 is life-threatening consequences, and Grade 5 is death related to the adverse event.
Time Frame
Up to Day 366

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
Inclusion Criteria: Signed informed consent for study. For women of childbearing potential: willing to engage in effective methods of contraception starting at least 28 days prior to vaccination and during the study. Willing to minimize blood and body fluid exposure to others (encourage abstinence, and hand hygiene; discourage contact with blood, vomit, feces without personal protective equipment (PPE) for at least 14 days following vaccine administration. Willing to forgo blood donation until 56 days following vaccination. Exclusion Criteria: At risk of travel-related or occupational exposure to Ebola virus such as through laboratory, clinical contact, field work, or in the judgment of the investigator. Received any Ebola vaccines or have history of Ebola Virus Disease (EVD). Current or previous diagnosis of immunocompromising condition such as human immunodeficiency virus or other immunosuppressive condition by receiving systemic immunosuppressants or immune-modifying drugs for >14 days in total within 6 months prior to screening (for corticosteroids: ≥ 10mg/day of prednisone or equivalent) or anticipates the need for immunosuppressive treatment at any time during participation in the study. Pregnant and/or breastfeeding (must have urine pregnancy test on the day of vaccination and during screening visit) Known allergy to any component of the rVSV∆G-ZEBOV-GP vaccine products (VSV, albumin, tris). History of severe local or systemic reactions to any vaccination. Received investigational drug within 5 half-lives or 28 days, whichever is longer, prior to study vaccination. Received or intends to receive vaccines within 28 days prior to or following study vaccination. Received immunoglobulins and/or any blood products within 120 days prior to study vaccination. Clinical evidence of systemic infection or other acute intercurrent illness (e.g. oral temp >38°C or > 100.4°F) less than 72 hours prior to study vaccination. Currently has symptomatic, acute, or unstable chronic disease requiring medical or surgical care, to include significant change in therapy or hospitalization, at the discretion of the investigator. History of excessive alcohol consumption, drug abuse, psychiatric conditions, social conditions, or occupational conditions that in the opinion of the investigator would preclude compliance with the study. Any condition that would limit the ability of the participant to meet protocol requirements or would place the participant at unreasonable risk in the opinion of the investigator.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Nadine Rouphael, MD
Phone
404-712-1435
Email
nroupha@emory.edu
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Nadine Rouphael, MD
Organizational Affiliation
Emory University
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Ali Ellebedy, PhD
Organizational Affiliation
Washington University School of Medicine
Official's Role
Study Chair
Facility Information:
Facility Name
The Hope Clinic of the Emory Vaccine Center
City
Decatur
State/Province
Georgia
ZIP/Postal Code
30030
Country
United States

12. IPD Sharing Statement

Plan to Share IPD
Yes
IPD Sharing Plan Description
De-identified data collected during the trial will be submitted to the National Center for Biotechnology Information (NCBI) on its GenBank and Sequence Read Archive (SRA) archives for public release upon publication of the findings of our studies. GenBank is the United States National Institutes of Health genetic sequence database, an annotated collection of all publicly available DNA sequences. SRA is an open access archive of minimally-processed read data from high throughput platforms.
IPD Sharing Time Frame
Data will become available for sharing upon publication of results for this study, with no end date.
IPD Sharing Access Criteria
Data will be available for sharing with anyone who wishes to access the data for any purpose. GenBank sequence records will be made available at https://ftp.ncbi.nih.gov/genbank/ or accessed using NCBI's E-utilities application programming interface (API). SRA sequence records will be made available using the SRA Toolkit API (https://github.com/ncbi/sra-tools/wiki) or on Amazon Web Services and Google Cloud Platform clouds (https://www.ncbi.nlm.nih.gov/sra/docs/sra-cloud/). Upon release, publicly accessible sequence data are searchable by accession number in website interfaces. NCBI also indexes the data to support text-based searches (e.g., by organism name) in websites and APIs.

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Immunology of Ebola Vaccine

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