EBV Vaccine for EBV Infection

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

25 Participants Needed

Trial Summary

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.

What data supports the effectiveness of the EBV gp350-Ferritin Vaccine, Matrix-M1 Adjuvant, Placebo Comparator, Placebo, Control, Inactive Control treatment for EBV infection?

Research shows that a similar EBV vaccine, which includes the gp350 protein, successfully produced antibodies in animals that blocked the virus from infecting cells. This suggests that the gp350 component in the vaccine could help protect against EBV infection. ^{1 2 3 4 5}

Is the EBV vaccine safe for humans?

The EBV vaccine has been tested in healthy adults and showed a good safety profile, with most symptoms being mild and within a clinically acceptable range. One serious adverse event was reported, but overall, the vaccine was well tolerated. ^{1 6 7 8 9}

How is the EBV gp350-Ferritin Vaccine with Matrix-M1 Adjuvant different from other treatments for Epstein-Barr virus?

The EBV gp350-Ferritin Vaccine with Matrix-M1 Adjuvant is unique because it uses a nanoparticle approach to display viral proteins, potentially enhancing the immune response compared to traditional vaccines. This vaccine aims to induce strong neutralizing antibodies to prevent EBV infection, which is not currently achievable with existing treatments, as there are no standard vaccines or therapies for EBV. ^{1 7 9 10 11}

What is the purpose of this trial?

Background: Epstein-Barr virus (EBV) causes most cases of infectious mononucleosis (mono). Mono can cause fatigue that lasts more than 6 months, and some people can have severe complications. EBV infection may also contribute to some cancers and autoimmune diseases. Currently, there are no approved therapies or vaccines for EBV infection. Objective: To test a vaccine against EBV. Eligibility: Healthy people aged 18 to 25 years. Design: Participants will be screened in 2 parts. They will have a blood test. If that test shows they have never had an EBV infection, they will have a second clinic visit. They will have a physical exam, with blood and urine tests. A cotton swab will be rubbed on their gums to collect saliva. Participants will receive 2 injections into a shoulder muscle. Some will receive the EBV vaccine. Others will receive a placebo; this contains harmless salt water with no vaccine. Participants will not know which one they are getting. The 2 injections will be 30 days apart. Participants will be asked to record any side effects or symptoms they have between visits. They can do this on paper or online. Participants will return for a follow-up visit 60 days after the first injection. They will have follow-up visits by phone or telehealth after 5 and 8 months. They will return for a physical exam after 13 months. They may come back for an optional physical exam after 2 years. Participants will come to the clinic if they become ill with an EBV infection during the study.

Research Team

Jessica R Durkee-Shock, M.D.

Principal Investigator

National Institute of Allergy and Infectious Diseases (NIAID)

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

References

1. United States pubmed.ncbi.nlm.nih.gov

A bivalent Epstein-Barr virus vaccine induces neutralizing antibodies that block infection and confer immunity in humanized mice. [2022]

2. Egypt pubmed.ncbi.nlm.nih.gov

Computer-Aided Design of an Epitope-Based Vaccine against Epstein-Barr Virus. [2018]

3. United States pubmed.ncbi.nlm.nih.gov

Phase I trial of a CD8+ T-cell peptide epitope-based vaccine for infectious mononucleosis. [2021]

4. United States pubmed.ncbi.nlm.nih.gov

Immunogenic particles with a broad antigenic spectrum stimulate cytolytic T cells and offer increased protection against EBV infection ex vivo and in mice. [2020]

5. United States pubmed.ncbi.nlm.nih.gov

Immunoinformatics Approach to Design Novel Subunit Vaccine against the Epstein-Barr Virus. [2022]

6. Netherlands 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. [2007]

7. Netherlands pubmed.ncbi.nlm.nih.gov

Immunization of cottontop tamarins and rabbits with a candidate vaccine against the Epstein-Barr virus based on the major viral envelope glycoprotein gp340 and alum. [2019]

8. United States pubmed.ncbi.nlm.nih.gov

Immunization with a Self-Assembled Nanoparticle Vaccine Elicits Potent Neutralizing Antibody Responses against EBV Infection. [2021]

9. Netherlands pubmed.ncbi.nlm.nih.gov

The need and challenges for development of an Epstein-Barr virus vaccine. [2021]

10. United States pubmed.ncbi.nlm.nih.gov

Vaccine Development for Epstein-Barr Virus. [2020]

11. Switzerland pubmed.ncbi.nlm.nih.gov

Epstein Barr Virus: Development of Vaccines and Immune Cell Therapy for EBV-Associated Diseases. [2021]