Ebola Vaccine Immunology

Recruiting at 1 trial location

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

Trial Summary

What is the purpose of this trial?

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.

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.

What data supports the effectiveness of the Ebola vaccine treatment rVSV-ZEBOV?

The rVSV-ZEBOV vaccine has shown to be effective in preventing Ebola virus disease in field studies, particularly in a trial conducted in Guinea, West Africa, where it was used to protect people who were in contact with confirmed Ebola cases. ^{1 2 3 4 5}

Is the Ebola vaccine rVSV∆G-ZEBOV-GP safe for humans?

The Ebola vaccine rVSV∆G-ZEBOV-GP, also known as Ervebo, has been tested in several studies and is generally considered safe for humans. These studies, which included healthy adults, found that the vaccine was well-tolerated with no serious safety concerns reported. ^{1 3 6 7 8}

What makes the rVSV-ZEBOV vaccine unique for treating Ebola?

The rVSV-ZEBOV vaccine is unique because it uses a live, weakened virus to deliver a protein from the Ebola virus, helping the body build immunity with just a single dose. This approach is different from other treatments that may require multiple doses or use different mechanisms to stimulate the immune response. ^{1 2 3 4 5}

Research Team

Nadine Rouphael, MD

Principal Investigator

Emory University

Ali Ellebedy, PhD

Principal Investigator

Washington University School of Medicine

Eligibility Criteria

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

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)

Treatment Details

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.

Participant Groups

Group I: Recombinant Vesicular Stomatitis Vaccine for Ebola (rVSV∆G-ZEBOV-GP) 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+

Findings from Research

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-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 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 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 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]

References

1. United States 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. [2020]

2. England 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!). [2022]

3. England 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. [2022]

4. England pubmed.ncbi.nlm.nih.gov

Durability of single-dose rVSV-ZEBOV vaccine responses: what do we know? [2019]

5. United States 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. [2020]

6. United States 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. [2023]

7. United States 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. [2018]

8. United States 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. [2018]