Safety and Immunogenicity of an Epstein-Barr Virus (EBV) gp350-Ferritin Nanoparticle Vaccine in Healthy Adults With or Without EBV Infection

NCT04645147 | Active Not Recruiting Phase 1 FDA Drug

• 2 other identifiers: 21000521-I-0005
• Study Type: interventional
• Target: 83
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

EBV; Epstein-Barr Virus Infection; Infectious Mononucleosis

Keywords

Infectious Mononucleosis; Neutralizing Antibody; CD4+ T cell response; Immune Response

Outcome Measures

Primary Outcomes (1)

• Local and systemic reactogenicity; unsolicited adverse events; serious adverse events; change in neutralizing antibody responses to EBV

  -Local reactogenicity: pain, tenderness, redness, bruising, swelling; Systemic reactogenicity symptoms: headache, muscle pain, fatigue, chills, oral temperature, joint pain, nausea/ vomiting, diarrhea; Change in log10 antibody response to EBV from baseline to 1 month after third dose of vaccine(Day 210) as measured by neutralization assay.

  Reactogenicity during the 7-day period after each dose; unsolicited adverse events up to 30 days after each dose; serious adverse events through 1 month after the third dose:; neutralizing antibody response one month after third dose

Secondary Outcomes (1)

• Change in antibody responses to EBV gp350; change in CD4+ T cell responses to EBV gp350

  Change in antibody responses and change in CD4 T cell responses at 1 month after third dose of vaccine

Study Arms (1)

EBV gp_350 Ferritin Vaccination

EXPERIMENTAL

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

Biological: EBV gp350-Ferritin Vaccine; Other: Matrix-M1

Interventions

EBV gp350-Ferritin Vaccine BIOLOGICAL

A 50 micrograms dose of EBV gp350-Ferritin vaccine will be administered intramuscularly for each vaccination at Days 0, 30, and 180 to all participants.

EBV gp_350 Ferritin Vaccination

Matrix-M1 OTHER

Each vaccine dose will consist of 50 micrograms of EBV gp350-Ferritin combined with 49 micrograms of Matrix-M1.

EBV gp_350 Ferritin Vaccination

Eligibility Criteria

• Age: 18 Years - 29 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• In order to be eligible to participate in this study, an individual must meet all of the following criteria:
• to 29 years old
• Screening procedures and evaluations performed no more than 30 days prior to scheduled administration of the first vaccine dose.
• Ability of subject to understand and the willingness to sign a written informed consent document.
• Stated willingness to comply with all study procedures and availability for the duration of the active phase of the study (approximately 18 months)
• 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 result.
• Subject 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. An FDA-approved inactivated, subunit or replication-defective vaccine (such as COVID-19, influenza,
• tetanus etc.) and/or a COVID-19 vaccine approved under emergency use authorization can be used \>=14 days before or \>=14 days after administration of the study vaccine.
• For females of reproductive potential who are sexually active with a male partner: 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.
• For males who are sexually active with partners of child-bearing potential: use of highly effective continuous contraception from Day 0 and agreement to continue use until 30 days after the last dose of vaccine.
• Contraceptive requirements: Because the effects of EBV gp350-Ferritin vaccine on the developing human fetus are unknown, sexually active female 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. Females of childbearing potential must have a negative pregnancy test before receiving each dose of the EBV gp350-Ferritin 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 (e.g. 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, path, or ring, then a barrier method (e.g. male/female 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, e.g. has undergone a vasectomy at least 6 months prior to the first dose of vaccine or is of the same sex as the participant.

You may not qualify if:

• An individual who meets any of the following criteria will be excluded from participation in this study:
• Women who are 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
• Any live attenuated vaccination within 30 days prior to first dose of vaccine
• Medically indicated subunit inactivated or replication-defective vaccines, e.g. influenza, pneumococcal, COVID-19 within 14 days of the 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.
• Participant has any of the following:
• Febrile illness within 14 days of the first dose of vaccine
• Obesity, in which any of the following are true:
• The deltoid muscle cannot be clearly identified
• Intramuscular (IM) vaccine administration/dosing may be compromised
• Presence of medical comorbidities such that enrollment is not in the best interests of the participant

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

Location

Related Publications (3)

• Cohen JI, Fauci AS, Varmus H, Nabel GJ. Epstein-Barr virus: an important vaccine target for cancer prevention. Sci Transl Med. 2011 Nov 2;3(107):107fs7. doi: 10.1126/scitranslmed.3002878.

  PMID: 22049067 BACKGROUND

• 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

Related Links

• NIH Clinical Center Detailed Web Page

MeSH Terms

Conditions

Epstein-Barr Virus Infections; Infectious Mononucleosis

Interventions

Matrix-M

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

Study Design

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

Study Record Dates

• First Submitted: November 25, 2020
• First Posted: November 27, 2020
• Study Start: March 29, 2022
• Primary Completion: July 1, 2025
• Study Completion (Estimated): July 1, 2026
• Last Updated: July 17, 2025

Record last verified: 2025-07-15

Data Sharing

• IPD Sharing: Will share
• Shared Documents: ICF, CSR
• Time Frame: Results from the Clinical Center Laboratory will be available within one to two weeks and will be discussed by the study team.
• Access Criteria: IPD will be shared with the patient. IPD will also be discussed with the study team. If collaborations are initiated the samples will be coded so that the collaborator does not know the names of the patients.

Locations

US (1)