Epstein-Barr Virus (EBV) gH/gL/gp42-Ferritin Nanoparticle Vaccine With or Without gp350-Ferritin in Healthy Adults With or Without EBV Infection

NCT06908096 | Recruiting Phase 1 FDA Drug

• 2 other identifiers: 10002288002288-I
• Study Type: interventional
• Target: 750
• Locations: 1 country
• Sites: 1

Brief Summary

Background: Epstein-Barr virus (EBV) is the primary cause of infectious mononucleosis, commonly known as mono. EBV infects more than 90% of the world s population. Mono can be serious, and it can lead to severe illnesses like cancer and autoimmune diseases. Researchers want to test vaccines that may help prevent EBV and associated diseases. Objective: To test two EBV vaccines: EBV gH/gL/gp42-ferritin and EBV gp350-ferritin. Eligibility: Healthy EBV-negative or EBV-positive people aged 18 to 29. Design: Participants will be screened. They will have a physical examination. They will give blood and saliva samples. They will receive 3 doses of the study vaccine as an injection in the shoulder muscle. They will get either one vaccine or a combination of both vaccines. Participants will get their first dose of the vaccine at visit 1, the second dose about 30 days later, and the final dose about 90 days after that. Participants will be given a memory aid so they can record any symptoms and side effects between visits. This can be done either on paper or online through a link that is emailed to them. There are 6 required in-person visits. There are also 2 optional visits. In between the in-person visits are 7 telehealth visits or phone calls. Each visit may take up to 4 hours. The study will last for about 17 months. Participants will have the option of staying in the study for an additional year.

Conditions

EBV; Mono; Epstein-Barr Virus Infection; Infectious Mononucleosis

Keywords

Infectious Mononucleosis; Neutralizing Antibody; Vaccine; EBV; Mono; Immune Response

Outcome Measures

Primary Outcomes (1)

• Local and systemic reactogenicity signs and symptoms during the 7-day period after each vaccination. Unsolicited AEs up to 30 days after each vaccination and SAEs through Day 150.

  To determine the safety of an adjuvanted EBV gH/gL/gp42-ferritin nanoparticle vaccine with or without gp350-ferritin nanoparticle in seronegative and seropositive healthy adults.

  Through Day 150

Secondary Outcomes (3)

• Change in log10 antibody response to EBV from baseline to 30 days after the last dose of vaccine (Day 150) as measured by the B cell neutralization assay.

  Through Day 150

• Change in log10 antibody response to EBV from baseline to 30 days after the last dose of vaccine (Day 150) as measured by the epithelial cell neutralization assay.

  Through Day 150

• ELISA-determined dilution for for antibodies to H. pylori and/or human ferritin on Day 0, Day 30, Day 60, and Day 150.

  Length of the study

Study Arms (2)

Dose escalation

EXPERIMENTAL

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

Biological: EBV gp350-ferritin vaccine with ALFQ adjuvant; Biological: EBV gH/gL/gp42-ferritin nanoparticle vaccine with ALFQ adjuvant

Randomization

EXPERIMENTAL

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.

Biological: EBV gp350-ferritin vaccine with ALFQ adjuvant; Biological: EBV gH/gL/gp42-ferritin nanoparticle vaccine with ALFQ adjuvant

Interventions

EBV gH/gL/gp42-ferritin nanoparticle vaccine with ALFQ adjuvant BIOLOGICAL

The adjuvanted gH/gL/gp42-ferritin nanoparticle vaccine is given with gp350-ferritin intramuscularly into the deltoid muscle at 0, 1, and 4 months.

Dose escalation; Randomization

EBV gp350-ferritin vaccine with ALFQ adjuvant BIOLOGICAL

The adjuvanted gH/gL/gp42-ferritin nanoparticle vaccine is given with gp350-ferritin intramuscularly into the deltoid muscle at 0, 1, and 4 months.

Dose escalation; Randomization

Eligibility Criteria

• Age: 18 Years - 29 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• To be eligible to participate in this study, an individual must meet all of the following criteria:
• to 29 years old.
• Able to provide informed consent.
• Willingness to allow storage of blood and saliva for future research.
• In good general health as evidenced by medical history, physical examination, and laboratory screening results.
• Participant is willing to forgo receipt of a licensed, live vaccine in the 30 days preceding each dose of vaccine or in the 30 days following each dose of vaccine. Any FDA-approved inactivated, subunit, or replication-defective vaccine (such as COVID-19, influenza, tetanus, etc.) can be used \>=14 days before or \>=14 days after administration of the study vaccine.
• Participants of reproductive potential who are sexually active with a partner who can impregnate them: use of highly effective continuous contraception for at least 30 days prior to Day 0 and agreement to continue use until 60 days after the last dose of vaccine.
• Contraceptive requirements: Because the effects of EBV gH/gL/gp42-FNP and EBV gp350-ferritin vaccines on the developing human fetus are unknown, sexually active participants of childbearing potential must agree to use highly effective contraception as outlined below before study entry and until 60 days after the last dose of vaccine. Participants of childbearing potential must have a negative pregnancy test before receiving each dose of the EBV gH/gL/gp42-FNP vaccine. During the course of the study, if a participant becomes pregnant or suspects they are pregnant, then they should inform the study staff and their primary care physician immediately.
• Acceptable forms of contraception are:
• Intrauterine device (IUD) or equivalent.
• Hormonal contraceptive (eg, consistent, timely, and continuous use of contraceptive pill, patch, ring, implant, or injection that has reached full efficacy prior to dosing). If the participant uses a contraceptive pill, patch, or ring, then a barrier method (eg, internal/external condom, cap, or diaphragm plus spermicide) must also be used at the time of potentially reproductive sexual activity.
• A stable, long-term monogamous relationship with a partner who does not pose any potential pregnancy risk, eg, has undergone a vasectomy at least 6 months prior to the first dose of vaccine or is of the same sex as the participant.
• A hysterectomy and/or a bilateral tubal ligation or bilateral oophorectomy.
• Acceptable forms of contraception for participants who can impregnate a partner include one of the following:
• External condom plus spermicide, used during sexual intercourse, even if the partner uses a contraceptive pill, patch, or ring.

You may not qualify if:

• An individual who meets any of the following criteria will be excluded from participation in this study:
• Pregnant, breastfeeding, or planning to become pregnant while participating through 60 days after the last dose of vaccine.
• Participant has received any of the following:
• More than 10 days of systemic immunosuppressive medications (\>=10 mg prednisone dose or its equivalent) or cytotoxic medication within the 30 days prior to first dose of vaccine or immunomodulating therapy within 180 days prior to first dose of vaccine.
• Blood products, including immunoglobulin products, within 120 days prior to first dose of vaccine.
• Investigational research agents within 30 days prior to first dose or planning to receive investigational products while on study.
• Allergy treatment with antigen injections, unless on a maintenance schedule of shots no more frequently than once per month.
• Prior participant in an EBV vaccine clinical trial.
• Participant has any of the following:
• Febrile illness within 14 days of the first dose of vaccine.
• Body habitus such that it is difficult to confirm location of the deltoid muscle for safe intramuscular injection.
• History of serious reactions to vaccines.
• Hereditary, acquired, or idiopathic forms of angioedema.
• Idiopathic urticaria within the past year.
• Asthma that is not well-controlled or required emergent care, urgent care, hospitalization, or intubation during the past 2 years or that requires the use of oral or intravenous steroids.

Sponsors & Collaborators

• National Institute of Allergy and Infectious Diseases (NIAID): lead

Study Sites (1)

National Institutes of Health Clinical Center

Bethesda, Maryland, 20892, United States

RECRUITING

Related Publications (3)

• Cohen JI. Epstein-barr virus vaccines. Clin Transl Immunology. 2015 Jan 23;4(1):e32. doi: 10.1038/cti.2014.27. eCollection 2015 Jan.

  PMID: 25671130 BACKGROUND

• Kanekiyo M, Bu W, Joyce MG, Meng G, Whittle JR, Baxa U, Yamamoto T, Narpala S, Todd JP, Rao SS, McDermott AB, Koup RA, Rossmann MG, Mascola JR, Graham BS, Cohen JI, Nabel GJ. Rational Design of an Epstein-Barr Virus Vaccine Targeting the Receptor-Binding Site. Cell. 2015 Aug 27;162(5):1090-100. doi: 10.1016/j.cell.2015.07.043. Epub 2015 Aug 13.

  PMID: 26279189 BACKGROUND

• Wei CJ, Bu W, Nguyen LA, Batchelor JD, Kim J, Pittaluga S, Fuller JR, Nguyen H, Chou TH, Cohen JI, Nabel GJ. A bivalent Epstein-Barr virus vaccine induces neutralizing antibodies that block infection and confer immunity in humanized mice. Sci Transl Med. 2022 May 4;14(643):eabf3685. doi: 10.1126/scitranslmed.abf3685. Epub 2022 May 4.

  PMID: 35507671 BACKGROUND

Related Links

• NIH Clinical Center Detailed Web Page

MeSH Terms

Conditions

Epstein-Barr Virus Infections; Infectious Mononucleosis

Condition Hierarchy (Ancestors)

Herpesviridae Infections; DNA Virus Infections; Virus Diseases; Infections; Tumor Virus Infections; Leukocyte Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Study Officials

• Jessica R Durkee-Shock, M.D.

  National Institute of Allergy and Infectious Diseases (NIAID)

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Jessica R Durkee-Shock, M.D.

CONTACT

(301) 761-6539; jessica.durkee-shock@nih.gov

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: OTHER
• Intervention Model: PARALLEL
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 2, 2025
• First Posted: April 3, 2025
• Study Start: May 29, 2025
• Primary Completion (Estimated): October 1, 2027
• Study Completion (Estimated): October 1, 2028
• Last Updated: May 6, 2026

Record last verified: 2026-04-30

Data Sharing

• IPD Sharing: Will share
• Shared Documents: ICF, CSR
• Time Frame: Data will be shared after conclusion of the trial and upon request by appropriate researchers.
• Access Criteria: Data will be shared in compliance with the NIH data sharing policy, the clinical protocol, and participant consent forms. Furthermore, sharing of data must also be approved by WRAIR.

Locations

US (1)