Ebola Vaccine Immunology

Recruiting at 2 trial locations

Overseen By Nadine Rouphael, MD, MSc

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Emory University

Must not be taking: Immunosuppressants, Immune-modifying drugs

Disqualifiers: Immunocompromising conditions, Pregnancy, Ebola exposure, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 4 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 1

30 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to test an Ebola vaccine that could enhance the immune system's response to the virus. Participants will receive a single dose of the vaccine, and some will also take a special type of water for 14 or 28 days to help researchers understand the body's response. The researchers seek healthy adults who have never been exposed to the Ebola virus and have not received an Ebola vaccine before. This study will evaluate the vaccine's effectiveness by monitoring the immune system's reaction over time. As a Phase 2 trial, this research measures the treatment's effectiveness in an initial, smaller group, offering participants a chance to contribute to important medical advancements.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, if you are on immunosuppressive drugs or plan to receive other vaccines, you may not be eligible to participate.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that the Ebola vaccine, rVSV∆G-ZEBOV-GP, is generally safe and well-tolerated. In earlier studies, participants often experienced common side effects such as pain at the injection site or mild symptoms like fever or headache. These side effects occurred more frequently than in those who received a placebo (a shot with no active vaccine). Importantly, no serious side effects were directly linked to the vaccine, suggesting it is safe for use. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

The Recombinant Vesicular Stomatitis Vaccine for Ebola (rVSV∆G-ZEBOV-GP) is unique because it uses a live, attenuated virus to deliver Ebola virus proteins, which can stimulate a strong immune response. Unlike traditional vaccines that often require multiple doses for effectiveness, this vaccine is designed to be effective with just a single dose. Additionally, two variations of this treatment involve the use of deuterium-labeled water, which could help researchers understand the body's immune response over time. This innovative approach has the potential to enhance our understanding of vaccine efficacy and improve future immunization strategies against Ebola.

What evidence suggests that this trial's treatments could be effective for Ebola?

Research shows that the Ebola vaccine, rVSV∆G-ZEBOV-GP, has promising results. In this trial, participants will receive the vaccine in different treatment arms. Studies confirm that this vaccine helps the body build a strong defense against the Ebola virus. Previous research found that the vaccine causes the body to produce antibodies, proteins that attack the virus. These antibodies can last for up to four years after vaccination. Overall, evidence suggests that this vaccine could effectively protect against the Ebola virus. ^{2 3 6 7 8}

Who Is on the Research Team?

Nadine Rouphael, MD

Principal Investigator

Emory University

Ali Ellebedy, PhD

Principal Investigator

Washington University School of Medicine

Are You a Good Fit for This Trial?

Healthy adults who can consent, agree to use contraception, minimize exposure of bodily fluids to others for at least 14 days post-vaccination, and avoid blood donation for 56 days. Excluded are those with acute or chronic diseases needing treatment, substance abuse issues, immunocompromising conditions or treatments within the past 6 months, pregnancy/breastfeeding women, known allergies to vaccine components.

Inclusion Criteria

You are willing to abstain from contact with potentially infectious bodily fluids and practice proper hand hygiene for a minimum of 14 days following vaccine administration.

You are willing to abstain from donating blood for a period of 56 days following vaccination.

You have consented to participate in the study.

Exclusion Criteria

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

I have not had any vaccines 28 days before or plan to within 28 days after the study vaccine.

I have not received blood products or immunoglobulins in the last 120 days.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Vaccination

Participants receive a single dose of the recombinant Vesicular Stomatitis Vaccine for Ebola (rVSV∆G-ZEBOV-GP)

1 day

1 visit (in-person)

Initial Follow-up

Participants are monitored for adverse events and immune response through blood samples, fine needle aspirates, core biopsies, and bone marrow aspirates

4 weeks

Multiple visits (in-person)

Long-term Follow-up

Participants are monitored for long-term immune response and safety, including antibody titers and adverse events

12 months

Periodic visits (in-person)

What Are the Treatments Tested in This Trial?

Interventions

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

Trial Overview The trial is testing a single dose of an Ebola vaccine (rVSV∆G-ZEBOV-GP) in 30 participants. It involves collecting blood samples and other biopsies before and after vaccination to study immune responses over time in different body tissues.

How Is the Trial Designed?

Group I: Recombinant Vesicular Stomatitis Vaccine for Ebola and Deuterium Labeled Water for 28 Days Experimental Treatment 2 Interventions

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 II: Recombinant Vesicular Stomatitis Vaccine for Ebola and Deuterium Labeled Water for 14 Days Experimental Treatment 2 Interventions

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 III: Recombinant Vesicular Stomatitis Vaccine for Ebola Experimental Treatment 1 Intervention

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).

Recombinant Vesicular Stomatitis Vaccine for Ebola (rVSV∆G-ZEBOV-GP) is already approved in European Union, United States, Canada for the following indications:

Approved in European Union as Ervebo for:

• Prevention of Ebola virus disease caused by Zaire ebolavirus in individuals 1 year of age and older

Approved in United States as Ervebo for:

• Prevention of Ebola virus disease caused by Zaire ebolavirus in individuals 12 months of age and older

Approved in Canada as rVSV-ZEBOV for:

• Prevention of Ebola virus disease caused by Zaire ebolavirus in individuals 18 years of age and older

Who Is Running the Clinical Trial?

Emory University

Lead Sponsor

Trials

1,735

Recruited

2,605,000+

Merck Sharp & Dohme LLC

Industry Sponsor

Trials

4,096

Recruited

5,232,000+

Chirfi Guindo

Merck Sharp & Dohme LLC

Chief Marketing Officer since 2022

Degree in Engineering from Ecole Centrale de Paris, MBA from New York University Stern School of Business

Robert M. Davis

Merck Sharp & Dohme LLC

Chief Executive Officer since 2021

JD from Northwestern University Pritzker School of Law, MBA from Northwestern University Kellogg Graduate School of Management, Bachelor's in Finance from Miami University

Washington University School of Medicine

Collaborator

Trials

2,027

Recruited

2,353,000+

Published Research Related to This Trial

The rVSV-ZEBOV vaccine demonstrated a remarkable 100% efficacy in preventing Ebola virus disease in individuals who received immediate vaccination, with no cases reported in this group after 10 days, compared to 16 cases in the delayed vaccination group.

The vaccine was found to be generally safe, with only one serious adverse event (a febrile episode) deemed causally related to the vaccination, indicating a favorable safety profile during the trial involving 7651 participants.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and effectiveness of an rVSV-vectored vaccine expressing Ebola surface glycoprotein: interim results from the Guinea ring vaccination cluster-randomised trial. Henao-Restrepo, AM., Longini, IM., Egger, M., et al.[2022]

The rVSV-ZEBOV vaccine shows strong persistence of Ebola virus glycoprotein-specific antibody responses for at least 2 years after a single dose, indicating long-term immunogenicity.

Higher vaccine doses are associated with better initial antibody persistence, but the relationship becomes less pronounced over time; additionally, vaccine-related arthritis is linked to both the persistence and strength of the antibody response.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Durability of single-dose rVSV-ZEBOV vaccine responses: what do we know? Huttner, A., Siegrist, CA.[2019]

In a study of 217 participants who received a single-dose rVSV-ZEBOV vaccine, high-dose recipients (10-50 million pfu) showed 100% seropositivity at 2 years, while 89% of low-dose recipients (300,000 pfu) remained seropositive, indicating that higher doses lead to better long-term immunity.

Antibody levels decreased significantly within the first 6 months post-vaccination but stabilized thereafter, suggesting that while initial antibody responses may wane, they can remain sufficient for long-term protection, especially in high-dose recipients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Determinants of antibody persistence across doses and continents after single-dose rVSV-ZEBOV vaccination for Ebola virus disease: an observational cohort study. Huttner, A., Agnandji, ST., Combescure, C., et al.[2020]

The rVSV-ZEBOV vaccine demonstrated 100% efficacy in preventing Ebola virus disease among vaccinated individuals, with no cases occurring 10 days or more after vaccination in both randomized and non-randomized clusters.

Out of 5837 individuals vaccinated, most reported mild adverse events, with only three serious adverse events linked to the vaccine, all of which resolved without lasting effects, indicating a favorable safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and effectiveness of an rVSV-vectored vaccine in preventing Ebola virus disease: final results from the Guinea ring vaccination, open-label, cluster-randomised trial (Ebola Ça Suffit!). Henao-Restrepo, AM., Camacho, A., Longini, IM., et al.[2022]

The rVSVΔG-ZEBOV-GP vaccine (ERVEBO®) effectively induced strong antibody responses in both children and adults after a single dose, with responses in children being non-inferior to those in adults, based on a study involving 1,602 participants.

Vaccine virus shedding was observed in 31.7% of vaccinated children but was time-limited, peaking by Day 7 and not occurring after Day 28 post-first dose, indicating a favorable safety profile for the vaccine.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Immunogenicity and vaccine shedding after 1 or 2 doses of rVZVΔG-ZEBOV-GP Ebola vaccine (ERVEBO®): Results from a phase 2, randomized, placebo-controlled trial in children and adults. Lee, AW., Liu, K., Lhomme, E., et al.[2023]

The rVSVΔG-ZEBOV-GP vaccine was generally well-tolerated in a study of 1197 participants, with increased rates of mild to moderate adverse events (AEs) like fever and joint pain compared to placebo, but no serious vaccine-related adverse events or deaths were reported.

Fever was observed in 20.2% of the combined lots group and 32.2% of the high-dose group, indicating that while the vaccine can cause some side effects, it is considered safe for individuals at risk for Ebola virus disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Six-Month Safety Data of Recombinant Vesicular Stomatitis Virus-Zaire Ebola Virus Envelope Glycoprotein Vaccine in a Phase 3 Double-Blind, Placebo-Controlled Randomized Study in Healthy Adults. Halperin, SA., Arribas, JR., Rupp, R., et al.[2018]

The rVSVΔG-ZEBOV-GP vaccine demonstrated strong immunogenicity, with over 94% of participants showing a significant antibody response 28 days post-vaccination, and this response persisted in over 91% of participants for 24 months.

The study, involving 1197 healthy adults, confirmed that different manufacturing lots of the vaccine were consistent in their immunogenicity, supporting the vaccine's safety and efficacy for further development.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Immunogenicity, Lot Consistency, and Extended Safety of rVSVΔG-ZEBOV-GP Vaccine: A Phase 3 Randomized, Double-Blind, Placebo-Controlled Study in Healthy Adults. Halperin, SA., Das, R., Onorato, MT., et al.[2020]

The rVSV∆G-ZEBOV-GP vaccine was found to be well tolerated among 513 healthy adults, with most adverse events being mild to moderate and occurring shortly after vaccination, particularly at higher doses.

The vaccine induced a strong immune response, with 95.7% of participants showing seroconversion and sustained antibody levels for up to one year, supporting the use of the 2×10^7 PFU dose for effective protection against Ebola.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and immunogenicity of the rVSV∆G-ZEBOV-GP Ebola virus vaccine candidate in healthy adults: a phase 1b randomised, multicentre, double-blind, placebo-controlled, dose-response study. Heppner, DG., Kemp, TL., Martin, BK., et al.[2018]

Citations

1. nejm.org nejm.org/doi/full/10.1056/NEJMoa1414216

A Recombinant Vesicular Stomatitis Virus Ebola Vaccine We present the final results of two phase 1 trials of an attenuated, replication-competent, recombinant vesicular stomatitis virus (rVSV)–based vaccine ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6816421/

Recombinant VSV Vaccines for WHO Priority Pathogens Safety and immunogenicity of the rVSV∆G-ZEBOV-GP Ebola virus vaccine candidate in healthy adults: a phase 1b randomised, multicentre, double-blind, placebo ...

3. thelancet.com thelancet.com/journals/laninf/article/PIIS1473-3099(17)30313-4/fulltext

Safety and immunogenicity of the rVSV∆G-ZEBOV-GP ... We report the safety and immunogenicity of the recombinant vesicular stomatitis virus-Zaire Ebola virus envelope glycoprotein vaccine (rVSV∆G- ...

4. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0264410X25008345

Long-term antibody responses to Ebola virus & vaccine vector Our results thus suggest a persistently detectable but strain-specific and slowly declining antibody response to EBOV up to 4 years after vaccination.

5. journals.asm.org journals.asm.org/doi/10.1128/jvi.01627-23

a VSV-vectored Ebola vaccine | Journal of Virology The rVSVΔG-ZEBOV-GP Ebola vaccine (ERVEBO; also referred to as V920 or VSV-EBOV) is a replication-competent, recombinant vesicular stomatitis ...

6. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/28549145/

Six-Month Safety Data of Recombinant Vesicular Stomatitis ... rVSVΔG-ZEBOV-GP was generally well-tolerated, with increased rates of injection-site and systemic AEs compared to placebo, and no vaccine-related SAEs or ...

7. sciencedirect.com sciencedirect.com/science/article/pii/S0163445324001713

Replication, safety and immunogenicity of the vectored ... Children experienced stronger and longer vector replication in plasma and shedding in saliva following rVSVΔG-ZEBOV-GP vaccination.

8. academic.oup.com academic.oup.com/jid/article-pdf/215/12/1789/24262177/jix189.pdf

Six-Month Safety Data of Recombinant Vesicular Stomatitis ... rVSVΔG-ZEBOV-GP was generally well-tolerated, with increased rates of injection-site and systemic AEs com- pared to placebo, and no vaccine- ...