Immunology of Ebola Vaccine

NCT ID: NCT06100913

Last Updated: 2026-01-22

Basic Information

• Recruitment Status: ACTIVE_NOT_RECRUITING
• Clinical Phase: PHASE2
• Total Enrollment: 30 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2024-08-06
• Study Completion Date: 2027-08-31

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.

Deuterium labeled water (D2O) or heavy water is chemically nearly the same as normal water (H2O) but the hydrogen atoms are of the heavy isotope deuterium (2H or D), in which the nucleus of the hydrogen atom contains a neutron in addition to the proton. Deuterium is not a radioactive isotope of hydrogen. When a person drinks D2O, it mixes with the body water, which is about 13 gallons in a 180 lb man. Many biological molecules use hydrogen atom from water as "ingredients" and will also use the deuterium from D2O if it is present in the body. Proteins, DNA, RNA, lipids, and other biomolecules become "labeled"; the faster the biomolecules are being synthesized, the more they become labeled with deuterium. The deuterium labeled molecules can be measured by sampling blood and body fluids. After isolating the biomolecules /cells of interest, a sensitive form of mass spectrometry is used to determine the extent of deuterium incorporation. All biomolecules synthesized prior to exposure to heavy water would have hydrogen exclusively (natural levels of deuterium are in trace quantities), while biomolecules synthesized after drinking heavy water will have a mix of hydrogen and deuterium.

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, the researchers 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.

The researchers will use stable isotope labeling to trace antigen-specific B cell responses to vaccination. In one cohort, participants will consume D2O for 14 days post-vaccination, labeling cells proliferating within the first 5-6 weeks. Antigen-specific plasmablasts and early memory B cells, collected at peak frequencies on days 7 and 14, will incorporate high levels of deuterium, measured via gas chromatography-mass spectrometry (GC-MS) analysis of DNA. Memory B cells and bone marrow plasma cells (BMPCs) will then be analyzed at later time points (Days 181 and 366) to assess deuterium dilution by newly divided cells. Another cohort, consuming D2O between days 57-85 post-vaccination, will label cells proliferating during the germinal center response. This approach enables the researchers to evaluate early versus later contributions to long-term memory B cells and antibody-secreting BMPCs.

Conditions

Ebola Virus Disease

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: BASIC_SCIENCE
• Blinding Strategy: NONE

Study Groups

Recombinant Vesicular Stomatitis Vaccine for Ebola

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).

Group Type: EXPERIMENTAL

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

Intervention Type: BIOLOGICAL

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.

Recombinant Vesicular Stomatitis Vaccine for Ebola and Deuterium Labeled Water for 14 Days

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) plus deuterium labeled water three times daily for 14 days from days 1-15.

Group Type: EXPERIMENTAL

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

Intervention Type: BIOLOGICAL

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.

Deuterium Labeled Water

Intervention Type: OTHER

An Emory Investigational Drug Service pharmacist will prepare sterile 50 ml aliquots of D2O with a tamper seal and stored at room temperature. Participants will be asked to drink a pre-measured volume of water three times a day and on days according to their assigned group schedule.

Recombinant Vesicular Stomatitis Vaccine for Ebola and Deuterium Labeled Water for 28 Days

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) plus deuterium labeled water three times daily for 28 days from days 57-85.

Group Type: EXPERIMENTAL

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

Intervention Type: BIOLOGICAL

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.

Deuterium Labeled Water

Intervention Type: OTHER

An Emory Investigational Drug Service pharmacist will prepare sterile 50 ml aliquots of D2O with a tamper seal and stored at room temperature. Participants will be asked to drink a pre-measured volume of water three times a day and on days according to their assigned group schedule.

Interventions

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

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.

Intervention Type: BIOLOGICAL

Deuterium Labeled Water

An Emory Investigational Drug Service pharmacist will prepare sterile 50 ml aliquots of D2O with a tamper seal and stored at room temperature. Participants will be asked to drink a pre-measured volume of water three times a day and on days according to their assigned group schedule.

Intervention Type: OTHER

Other Intervention Names

Ervebo; Heavy water

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 30 days prior to and for the duration of study participation.

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, rice protein).
• 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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Washington University School of Medicine

OTHER

Sponsor Role: collaborator

Merck Sharp & Dohme LLC

INDUSTRY

Sponsor Role: collaborator

Emory University

OTHER

Sponsor Role: lead

Responsible Party

Nadine Rouphael

Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Nadine Rouphael, MD

Role: PRINCIPAL_INVESTIGATOR

Emory University

Ali Ellebedy, PhD

Role: STUDY_CHAIR

Washington University School of Medicine

Locations

The Hope Clinic of the Emory Vaccine Center

Decatur, Georgia, United States

Washington University in St. Louis

St Louis, Missouri, United States

Countries

United States

Other Identifiers

STUDY00006747

Identifier Type: -

Identifier Source: org_study_id