EBV Vaccine for EBV Infection

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

Age: 18 - 65

Sex: Any

Trial Phase: Phase 1

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

Must not be taking: Immunosuppressants, Cytotoxic, Blood products, others

Disqualifiers: Pregnancy, Asthma, Diabetes, Hypertension, others

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

Compensation: Varies

Number of Visits: 12

750 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to test two new vaccines that might help prevent infections from the Epstein-Barr virus (EBV), which can cause mono and other serious illnesses. Researchers seek to determine if these vaccines can protect people from EBV and its complications. The trial is recruiting healthy individuals aged 18 to 29 who have either never had EBV or have had it. Participants will receive three doses of either one or both vaccines and must attend several in-person and virtual check-ups over 17 months.

As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive these new vaccines.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, you cannot have taken certain immunosuppressive or cytotoxic medications within 30 days before the first vaccine dose, and you should not receive investigational products while on the study.

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

Research has shown that the EBV gH/gL/gp42-ferritin nanoparticle vaccine is currently undergoing safety testing. Recipients of this vaccine have demonstrated a strong immune response, which is encouraging. However, detailed safety data from human trials remains limited due to the early stage of testing.

For the EBV gp350-ferritin vaccine, earlier studies have examined its safety and immune effects. Initial trials indicated it is generally safe for healthy adults, with most participants experiencing no major side effects.

Both vaccines are in the early phases of human testing, with the primary goal of assessing safety. This involves closely monitoring for any side effects or issues. While these vaccines appear promising in terms of safety, further information is needed for confirmation. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these EBV vaccines because they target the virus in new and innovative ways. Unlike standard treatments that primarily focus on managing symptoms, these vaccines aim to prevent the infection entirely. The EBV gH/gL/gp42-ferritin nanoparticle vaccine and the gp350-ferritin vaccine use a nanoparticle delivery system, which could enhance the immune response and potentially offer stronger, longer-lasting protection. By focusing on these unique viral proteins, the vaccines could provide a more effective defense against EBV compared to existing options.

What evidence suggests that this trial's vaccines could be effective for preventing EBV infection?

Research has shown that the EBV gH/gL/gp42-ferritin nanoparticle vaccine, one of the treatments studied in this trial, could help prevent Epstein-Barr virus (EBV) infections. Studies in mice and non-human primates found that this vaccine can create antibodies that stop the virus from entering cells, which is key to preventing infection. Similarly, the EBV gp350-ferritin vaccine, another treatment option in this trial, has also shown positive results. In animal studies, this vaccine successfully produced strong antibodies that can identify and fight EBV. These early findings suggest that both vaccines might prevent EBV infections, offering hope for reducing the risk of diseases linked to this virus. ^{1 2 4 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 adults, both with and without prior Epstein-Barr Virus (EBV) infection, are eligible for this trial. The study is designed to assess the safety of a new EBV vaccine given in three doses over four months.

Inclusion Criteria

Participants of reproductive potential who are sexually active with a partner who can impregnate them must use highly effective continuous contraception for at least 30 days prior to Day 0 and agree to continue use until 60 days after the last dose of vaccine

Able to provide informed consent

Laboratory criteria within 30 days or less prior to enrollment: Hemoglobin, white blood cell count, total lymphocyte count, platelet count, alanine aminotransferase, and serum IgG within specified ranges

Exclusion Criteria

Pregnant, breastfeeding, or planning to become pregnant while participating through 60 days after the last dose of vaccine

Received blood products, investigational research agents, allergy treatment with antigen injections, or been a prior participant in an EBV vaccine clinical trial within specified time frames

Any medical, psychiatric, or social condition that, in the judgement of the investigator, is a contraindication to protocol participation or impairs the participant's ability to give informed consent

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Dose Escalation

Initial phase where 9 EBV-seropositive individuals receive varying doses of the vaccine to assess safety

1 month

3 visits (in-person)

Randomization

Participants receive 3 doses of the vaccine at 0, 1, and 4 months

4 months

6 visits (in-person), 7 telehealth visits or phone calls

Follow-up

Participants are monitored for safety and effectiveness after the last dose of the vaccine

12 months

2 optional visits (in-person)

Open-label Extension (optional)

Participants may opt into continuation of monitoring for an additional year

12 months

What Are the Treatments Tested in This Trial?

Interventions

• EBV gH/gL/gp42-ferritin nanoparticle vaccine
• EBV gp350-ferritin vaccine

Trial Overview The trial tests two EBV vaccines combined with an adjuvant: one includes gH/gL/gp42-ferritin nanoparticle alone, while the other adds gp350-ferritin. Participants will receive vaccinations at the start, after one month, and after four months.

How Is the Trial Designed?

Group I: Randomization Experimental Treatment 2 Interventions

In the randomization phase, twenty-four EBV-seropositive individuals will be randomized in a 1:1 ratio to receive either 3 doses of adjuvanted gH/gL/gp42-ferritin alone or adjuvanted gH/gL/gp42-ferritin + gp350-ferritin nanoparticle.

Group II: Dose escalation Experimental Treatment 2 Interventions

There will be an initial dose escalation phase comprised of 9 EBV seropositive individuals.

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

In a study of asymptomatic infants in Kisumu, Kenya, researchers found that coinfection with both EBV-1 and EBV-2 was common, which affected the antibody response, particularly resulting in lower levels of anti-gp350 IgA antibodies.

The lower levels of anti-gp350 IgA in coinfected infants suggest that these antibodies are crucial for preventing secondary infections, highlighting the need for an EBV vaccine that addresses both strains to effectively protect populations at high risk for Burkitt lymphoma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Differences in the Epstein-Barr Virus gp350 IgA Antibody Response Are Associated With Increased Risk for Coinfection With a Second Strain of Epstein-Barr Virus. Smith, NA., Baresel, PC., Jackson, CL., et al.[2020]

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]

Citations

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

NCT06908096 | Epstein-Barr Virus (EBV) gH/gL/gp42- ... This is a phase 1 study to evaluate the safety of a 3-dose vaccination regimen of an adjuvanted EBV gH/gL/gp42-ferritin nanoparticle vaccine with or without ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6660903/

Immunization with components of the viral fusion apparatus ... Bu et al. showed that an EBV nanoparticle vaccine elicits antibodies to EBV gH/gL and gp42 in mice and non-human primates that inhibit the viral fusion ...

3. nature.com nature.com/articles/s41541-022-00587-6

Urgency and necessity of Epstein-Barr virus prophylactic ... Immunization with a self-assembling nanoparticle vaccine displaying EBV gH/gL protects humanized mice against lethal viral challenge. Cell ...

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

A self-assembled nanoparticle vaccine elicits effective ... Conclusion: These data indicate that the L350–ferritin nanoparticle vaccine candidate has considerable potential application in preventing EBV ...

5. sciencedirect.com sciencedirect.com/science/article/pii/S2666379122001902

Immunization with a self-assembling nanoparticle vaccine ... A nanoparticle displaying 60 copies of gH/gL elicits antibodies that protect against lethal EBV challenge in humanized mice, whereas antibodies elicited by ...

6. trialx.com trialx.com/clinical-trials/listings/316264/epstein-barr-virus-ebv-ghglgp42-ferritin-nanoparticle-vaccine-with-or-without-gp350-ferritin-in-healthy-adults-with-or-without-ebv-infection/

Epstein-Barr Virus (EBV) gH/gL/gp42-Ferritin Nanoparticle ... This is a phase 1 study to evaluate the safety of a 3-dose vaccination regimen of an adjuvanted EBV gH/gL/gp42-ferritin nanoparticle vaccine ...

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12360862/

A bivalent Epstein-Barr virus vaccine induces neutralizing ... We have previously shown that a nanoparticle (NP)-based gp350 vaccine elicited protective immunity (16), and gH/gL and gH/gL/g42 NP vaccines induced potent ...