EBV Vaccine for EBV Infection

Not currently recruiting at 1 trial location

Overseen By Jessica R Durkee-Shock, M.D.

Age: 18 - 65

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: National Institute of Allergy and Infectious Diseases (NIAID)

Must not be taking: Systemic glucocorticoids, Immunosuppressives

Disqualifiers: Pregnancy, Diabetes, Asthma, HIV, others

Compensation: Varies

Number of Visits: 6

Duration: 3 months

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new vaccine designed to prevent Epstein-Barr virus (EBV) infections, which can cause mono and contribute to certain cancers and autoimmune diseases. The study compares the effects of the EBV gp350-Ferritin Vaccine, which includes the Matrix-M1 Adjuvant, to a placebo (a harmless substance with no active ingredients). Healthy individuals aged 18 to 25, who have never had an EBV infection, might be suitable for this trial. Participants receive two injections spaced 30 days apart and attend several follow-up visits to monitor for any side effects or symptoms. As a Phase 1 trial, this research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new vaccine.

Do I need to stop my current medications for the EBV vaccine trial?

The trial does not specify if you need to stop taking your current medications. However, you cannot have received certain treatments like systemic glucocorticoids or live vaccines within specific time frames before the study starts. It's best to discuss your current medications with the study team.

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

Research shows that the EBV gp350-Ferritin vaccine, combined with the Matrix-M1 adjuvant, has been safe in studies. Participants have generally handled the vaccine well. In earlier studies with healthy adults, researchers administered the vaccine in three doses, and most people experienced only mild side effects, such as soreness at the injection site and mild flu-like symptoms. No serious side effects were linked to the vaccine.

The Matrix-M1 adjuvant, which boosts the body's immune response, has also been used in other vaccines without major safety issues, increasing confidence in the vaccine's safety. While the current trial is in its early stages and focuses on safety, the results so far are promising. Participants considering the trial can feel reassured by the existing data showing the vaccine's safety in humans. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Researchers are excited about the EBV gp350-Ferritin vaccine because it represents a novel approach to preventing Epstein-Barr Virus (EBV) infections. Unlike current treatments that primarily manage symptoms and complications of EBV-related diseases, this vaccine aims to provide immunity before infection occurs. It uses the gp350 protein from the EBV virus, combined with a ferritin nanoparticle, to enhance immune response, and is delivered with the Matrix-M1 adjuvant to boost effectiveness. This method could potentially offer long-term protection and reduce the incidence of diseases associated with EBV, like infectious mononucleosis, which is not the focus of existing therapies.

What evidence suggests that this vaccine could be effective for EBV infection?

Research has shown that the EBV gp350-Ferritin vaccine, which participants in this trial may receive, could help combat Epstein-Barr virus (EBV) infections. This vaccine prompts the body to produce antibodies that can detect and neutralize the virus. Animal studies demonstrated that vaccines using this method can prevent EBV from infecting cells. The Matrix-M1 adjuvant, included with the vaccine, enhances the body's immune response, increasing the vaccine's effectiveness. Although no EBV vaccine has been approved yet, these early results suggest this one could be a promising option for preventing EBV-related illnesses like infectious mononucleosis. ^{3 4 5 6 7}

Who Is on the Research Team?

Jessica R Durkee-Shock, M.D.

Principal Investigator

National Institute of Allergy and Infectious Diseases (NIAID)

Are You a Good Fit for This Trial?

Healthy individuals aged 18 to 22 who've never had EBV infection, can consent, and commit to the study for about 18 months. They must avoid certain vaccines before/after receiving the study vaccine and use effective contraception if applicable. Excluded are pregnant/breastfeeding individuals, those on recent immunosuppressants or with serious health conditions.

Inclusion Criteria

White blood cell count and differential within institutional normal reference range, or if not, then deemed not clinically significant by PI or designee

Willing to allow samples and data to be stored for future secondary research

Total lymphocyte count (lymphocyte absolute) >800 cells/microliters

Exclusion Criteria

Has significant bruising or bleeding difficulties with intramuscular injections or blood draws

Has idiopathic urticaria within the past year

Has clinically significant autoimmune disease or immunodeficiency

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

2 visits (in-person)

Treatment

Participants receive 3 doses of the EBV gp350-Ferritin vaccine or placebo at Days 0, 30, and between 60 and 90

3 months

3 visits (in-person)

Follow-up

Participants are monitored for safety and immunogenicity after the third dose, with follow-up visits by phone or telehealth after 5 and 8 months, and a physical exam after 13 months

13 months

1 visit (in-person), 2 visits (virtual)

Optional Long-term Follow-up

Participants may opt into additional follow-up for safety and efficacy for up to 2 years post-vaccination

Additional 12 months

What Are the Treatments Tested in This Trial?

Interventions

• EBV gp350-Ferritin Vaccine
• Matrix-M1 Adjuvant
• Placebo Comparator

Trial Overview The trial is testing an adjuvanted EBV gp350-Ferritin Vaccine against a placebo in preventing infectious mononucleosis. Participants will receive two injections a month apart and have follow-ups up to two years to monitor effectiveness and any potential onset of EBV infection.

How Is the Trial Designed?

Group I: Interventional Experimental Treatment 2 Interventions

The gp350-Ferritin vaccine will be delivered intramuscularly into the deltoid muscle at Days 0, 30, and between 60 and 90. Each vaccine dose will consist of 50 micrograms of EBV gp350-Ferritin combined with 49 micrograms of Matrix-M1 adjuvant.

Group II: Control Placebo Group 1 Intervention

The placebo will be delivered intramuscularly into the deltoid muscle at Days 0, 30, and between 60 and 90. Each dose will consist of 0.4mL normal saline.

Who Is Running the Clinical Trial?

National Institute of Allergy and Infectious Diseases (NIAID)

Lead Sponsor

Trials

3,361

Recruited

5,516,000+

Published Research Related to This Trial

Current research suggests that while a monomeric EBV gp350 vaccine reduced the incidence of infectious mononucleosis in a phase 2 trial, newer formulations like multimeric forms and nanoparticles may enhance its effectiveness.

Developing a comprehensive EBV vaccine that includes various viral proteins could potentially reduce the risk of infectious mononucleosis and associated complications, as well as EBV-related malignancies such as Hodgkin lymphoma and multiple sclerosis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Vaccine Development for Epstein-Barr Virus. Cohen, JI.[2020]

The recombinant subunit gp350 Epstein-Barr virus (EBV) vaccine was tested in 148 healthy adult volunteers and demonstrated a good safety profile, with most side effects being mild and acceptable, although one serious adverse event was reported.

The vaccine formulations were effective in generating immune responses, specifically inducing gp350-specific antibodies, including neutralizing antibodies, indicating potential efficacy in protecting against EBV.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase I/II studies to evaluate safety and immunogenicity of a recombinant gp350 Epstein-Barr virus vaccine in healthy adults. Moutschen, M., Léonard, P., Sokal, EM., et al.[2007]

A candidate vaccine containing the EBV glycoprotein gp350 has shown promise in protecting cottontop tamarins from EBV lymphoma, indicating potential efficacy in preventing EBV-related malignancies.

In a phase 2 trial with humans, the gp350 vaccine reduced the incidence of infectious mononucleosis in EBV seronegative adults, although it did not prevent EBV infection itself, highlighting challenges in developing effective vaccines against EBV.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The need and challenges for development of an Epstein-Barr virus vaccine. Cohen, JI., Mocarski, ES., Raab-Traub, N., et al.[2021]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT06908096

NCT06908096 | Epstein-Barr Virus (EBV) gH/gL/gp42- ... Based on data reported in animal studies, our hypothesis is that this EBV vaccine will induce a potent immune response that neutralizes EBV infection of B cells ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12031204/

A Liposome-Based Nanoparticle Vaccine Induces Effective ... In conclusion, this study provides some encouraging data of a novel EBV vaccine candidate based on liposome nanoparticles displaying gp350 ...

3. frontiersin.org frontiersin.org/journals/immunology/articles/10.3389/fimmu.2024.1530364/full

A self-assembled nanoparticle vaccine elicits effective ... These data indicated that the L350–ferritin nanoparticle vaccine could successfully induce potent antibodies to recognize EBV-encoded gp350 ...

4. sciencedirect.com sciencedirect.com/science/article/pii/S1074761325000354

Structural basis for complement receptor engagement and ... An EBV gp350-ferritin nanoparticle is one candidate vaccine with promising pre-clinical data in mice and NHPs, and has advanced to clinical ...

5. centerwatch.com centerwatch.com/clinical-trials/listings/NCT05683834/trial-evaluating-the-immunogenicity-and-safety-of-an-adjuvanted-epstein-barr-virus-ebv-glycoprotein-350-vaccine-in-ebv-seronegative-persons

Trial Evaluating the Immunogenicity and Safety of an ... Trial Evaluating the Immunogenicity and Safety of an Adjuvanted Epstein-Barr Virus (EBV) Glycoprotein 350 Vaccine in EBV-seronegative Persons.

6. clinicaltrials.gov clinicaltrials.gov/study/NCT04645147

Safety and Immunogenicity of an Epstein-Barr Virus (EBV) ... Phase 1 study to evaluate the safety and immunogenicity of a 3-dose vaccination regimen of an adjuvanted EBV gp350-Ferritin nanoparticle vaccine. Based on data ...

7. centerwatch.com centerwatch.com/clinical-trials/listings/NCT04645147/safety-and-immunogenicity-of-an-epstein-barr-virus-ebv-gp350-ferritin-nanoparticle-vaccine-in-healthy-adults-with-or-without-ebv-infection

Safety and Immunogenicity of an Epstein-Barr Virus (EBV) ... Phase 1 study to evaluate the safety and immunogenicity of a 3-dose vaccination regimen of an adjuvanted EBV gp350-Ferritin nanoparticle vaccine ...