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, Obesity, Diabetes, Hypertension, others

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

Compensation: Varies

Number of Visits: 9

83 Participants Needed

Trial Summary

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 medications like systemic immunosuppressive drugs or live vaccines shortly before the trial starts.

What data supports the effectiveness of the EBV gp350-Ferritin Nanoparticle Vaccine treatment for EBV infection?

Research shows that a similar EBV vaccine using gp350 on nanoparticles can produce strong immune responses in animals, blocking the virus from infecting cells. This suggests that the gp350-Ferritin Nanoparticle Vaccine might also be effective in preventing EBV infection. ^{1 2 3 4 5}

How does the EBV gp350-Ferritin Nanoparticle Vaccine differ from other treatments for EBV infection?

The EBV gp350-Ferritin Nanoparticle Vaccine is unique because it uses a nanoparticle design to present multiple copies of the gp350 protein, which is a major target for neutralizing antibodies, potentially offering stronger protection against EBV infection compared to traditional monomeric vaccines. This approach is novel as there are currently no vaccines or treatments available for EBV infection. ^{1 2 6 7 8}

What is the purpose of this trial?

Background: Epstein-Barr virus (EBV) causes most cases of infectious mononucleosis (mono). Up to 1 in 10 people who get mono can have fatigue that lasts more than 6 months. One out of 100 people can have severe complications. EBV is also associated with several types of cancer. Researchers want to test an EBV vaccine. Objective: To test the safety of and immune response to a new vaccine against EBV. Eligibility: Healthy adults ages 18-29 Design: Participants will be screened with a medical history and physical exam. They will give a blood sample. Screening tests will be repeated during the study. Participants will get a dose of the study vaccine as an injection in a muscle in the upper arm. They will be observed for 30 to 60 minutes. Blood pressure, heart rate, breathing rate, and temperature will be checked. The injection site will be examined. Participants will get a diary card. They will write down any side effects they have after the vaccine dose, or they may use an electronic diary card. Participants will be asked to write down or enter any important medical events that may occur at any time during the study. Participants will get a vaccine dose at 2 more study visits. They will have 4 follow-up visits at different times after a vaccine dose. Participants will have 6 telephone calls in between the in-person visits. They will also have 1 telephone call 1 year after the third dose of vaccine. If possible, this visit can occur in person. Participation will last about 18 months. There is an optional in-person visit or telephone call 2 years after the third dose of vaccine.

Research Team

Jessica R Durkee-Shock, M.D.

Principal Investigator

National Institute of Allergy and Infectious Diseases (NIAID)

Eligibility Criteria

Healthy adults aged 18-29 can join this trial to test a new EBV vaccine. They must be in good health, not planning to receive other live vaccines around the study period, and willing to use effective contraception. People with severe reactions to vaccines, certain chronic diseases like uncontrolled asthma or diabetes, or those on immunosuppressive drugs cannot participate.

Inclusion Criteria

My partner uses effective birth control or has had surgery to prevent pregnancy.

I use hormonal birth control and a barrier method during sex.

I am using or agree to use effective birth control during and 60 days after the vaccine study.

Exclusion Criteria

My asthma has been severe, needing emergency care or steroids in the last 2 years.

My cancer is active or likely to come back during the study.

I haven't taken strong immune system medications or cancer drugs in the last month.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Vaccination

Participants receive 3 doses of the EBV gp350-Ferritin nanoparticle vaccine at 0, 1, and 6 months

6 months

3 visits (in-person)

Follow-up

Participants are monitored for safety and immune response, including local and systemic reactogenicity, adverse events, and antibody response

12 months

4 visits (in-person), 6 telephone calls

Long-term Follow-up (optional)

Participants have the option to be followed for an additional year to monitor long-term safety and immune response

12 months

1 visit (in-person or telephone)

Treatment Details

Interventions

• EBV gp350-Ferritin Nanoparticle Vaccine

Trial Overview The trial is testing the safety and immune response of an Epstein-Barr Virus (EBV) gp350-Ferritin nanoparticle vaccine with Matrix-M1 adjuvant in healthy young adults. Participants will get three doses of the vaccine over several months and have follow-ups for about 18 months.

Participant Groups

Group I: EBV gp_350 Ferritin Vaccination Experimental Treatment 2 Interventions

Adult participants with or without prior EBV infection will receive 3 doses of vaccine

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

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]

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

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

3. England pubmed.ncbi.nlm.nih.gov

Urgency and necessity of Epstein-Barr virus prophylactic vaccines. [2022]

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

A gB nanoparticle vaccine elicits a protective neutralizing antibody response against EBV. [2023]

5. England pubmed.ncbi.nlm.nih.gov

Lymph node targeted multi-epitope subunit vaccine promotes effective immunity to EBV in HLA-expressing mice. [2023]

6. United States 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. [2020]

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

Vaccine Development for Epstein-Barr Virus. [2020]

8. Netherlands pubmed.ncbi.nlm.nih.gov

Recombinant Epstein-Barr virus glycoprotein 350 as a serological antigen. [2021]