Safety and Immunogenicity of an Epstein-Barr Virus (EBV) gp350-Ferritin Nanoparticle Vaccine in Healthy Adults

NCT04645147 | Completed Phase 1 Results 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 (8)

• Number of Participants With Solicited Local Adverse Events (AEs)

  Number of participants with at least one solicited local adverse events occurring within seven days of each vaccine dose administration. Local reactogenicity included injection site pain, injection site redness, injection site bruising, and injection site swelling. Adverse events were captured by investigator examination and history from participants.

  During the 7-day period after each dose of vaccine

• Number of Participants With Solicited Local Adverse Events (AEs) (by Severity)

  The severity of local adverse event was graded using the Toxicity Grading Scale for Healthy Adult and Adolescent Volunteers Enrolled in Preventive Clinical Trials. Grade 1: Pain = does not interfere with activity; Tenderness = mild discomfort to touch; Erythema/Redness = 2.5-5 cm; Induration/Swelling = 2.5-5 cm and does not interfere with activity Grade 2: Pain = Repeated use of non-narcotic pain reliever \> 24 hours or interferes with daily activity; Tenderness= Discomfort with movement; Erythema/Redness = 5.1-10 cm; Induration/Swelling = 5.1-10 cm and interferes with activity Grade 3: Pain = Any use of narcotic pain reliever or prevents daily activity; Tenderness = Significant discomfort at rest; Erythema/Redness = \> 10 cm; Induration/Swelling = \> 10 cm or prevents daily activity Grade 4: Pain = Emergency room (ER) visit or hospitalization; Tenderness = ER visit or hospitalization; Erythema/Redness = Necrosis or exfoliative dermatitis; induration/Swelling = Necrosis

  During the 7-day period after each dose of vaccine

• Number of Participants With Solicited Systemic Adverse Events (AEs)

  Number of participants with solicited systemic adverse events occurring within seven days of each vaccine dose administration. Systemic reactogenicity events included headache, muscle pain, fatigue, chills, fever, joint pain, nausea, vomiting, and diarrhea. Adverse events were captured by investigator examination and history from participants.

  During the 7-day period after each dose of vaccine

• Number of Participants With Solicited Systemic Adverse Events (AEs) (by Grade)

  The severity of systemic adverse events occurring after the administration of each vaccine dose was assessed using the grading scale below: Grade 1: Fever = 37.5\^oC-37.9\^oC; Fatigue, Headache, Myalgia = No interference with activity; Nausea = no interference with activity or 1-2 episodes/hour Grade 2: Fever = 38\^oC-38.4\^oC; Fatigue, Myalgia = Some interference with activity; Headache = Repeated use of non-narcotic pain reliever \> 24 hours or some interference with activity; Nausea = Some interference with activity or \> 2 episodes/24 hours Grade 3: Fever = 38.5\^oC-39.5\^oC; Fatigue = Prevents daily activity; Headache =Significant; any use of narcotic pain reliever or prevents daily activity; Myalgia =Significant; prevents daily activity; Nausea = Prevents daily activity, requires outpatient intravenous hydration Grade 4: Fever = \> 39.5\^oC; Fatigue, Headache, Myalgia = Emergency room (ER) visit or hospitalization; Nausea = ER visit or hospitalization for hypotensive shock

  During the 7-day period after each dose of vaccine

• Number of Related Serious Adverse Events (AEs)

  Number of related serious adverse events (AEs) based on the Toxicity Grading Scale for Healthy Adult and Adolescent Volunteers Enrolled in Preventive Clinical Trials. Serious adverse event is defined as any local or systemic adverse event that * is a life-threatening event, or * an AE that requires inpatient hospitalization or prolongs an existing hospitalization, or * results in a persistent or significant incapacity, or * substantial disruption of the ability to conduct normal life functions, or * is a congenital anomaly/birth defect/miscarriage/still birth, or -- results in death

  Within one month after the third dose of vaccine (Day 180 through day 210)

• Number of Related Unsolicited Adverse Events

  Number of related unsolicited adverse events (AEs) occurring within 30 days of each vaccine dose administration. Unsolicited adverse event is defined as an adverse event that is not specifically asked.

  Within 30 days after each dose of vaccine

• Number of Unrelated Unsolicited Adverse Events

  Number of related unsolicited adverse events (AEs) occurring within 30 days of each vaccine dose administration. Unsolicited adverse event is defined as an adverse event that is not specifically asked.

  Within 30 days after each dose of vaccine

• Change in Neutralizing Antibody Responses to Epstein-Barr Virus (EBV) gp350-Ferritin Vaccine

  Change in log10 neutralizing antibody response to Epstein-Barr Virus (EBV) gp350-Ferritin vaccine from day 0 (baseline) to 30 days (Day 210) after the third dose of vaccine as measured by neutralization assay. Serum titer levels were analyzed as geometric means with 95% confidence intervals. Change = 30 days compared to baseline.

  Day 0 and Day 210

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 (2)

Epstein-Barr Virus (EBV) seronegative participants

EXPERIMENTAL

Participant seronegative for Epstein-Barr Virus (EBV) infection received three doses of the EBV gp350-Ferritin Vaccine 50 µg intramuscularly on study days 0, 30, and 180 with follow-up visits occurring after each dose of vaccine. In addition to vaccine dosing days, mandatory in-person visits occurred in the first week after the first dose of vaccine, one month after the second and third doses of vaccine, and six months after the third dose of vaccine.

Biological: EBV gp350-Ferritin Vaccine

Epstein-Barr Virus (EBV) seropositive participants

EXPERIMENTAL

Participant seropositive for Epstein-Barr Virus (EBV) infection received three doses of the EBV gp350-Ferritin Vaccine 50 µg intramuscularly on study days 0, 30, and 180 with follow-up visits occurring after each dose of vaccine. In addition to vaccine dosing days, mandatory in-person visits occurred in the first week after the first dose of vaccine, one month after the second and third doses of vaccine, and six months after the third dose of vaccine.

Biological: EBV gp350-Ferritin Vaccine

Interventions

EBV gp350-Ferritin Vaccine BIOLOGICAL

Each vaccine dose will consist of 50 micrograms of EBV gp350-Ferritin combined with 49 micrograms of Matrix-M1 adjuvant administered intramuscularly for each vaccination at Days 0, 30, and 180..

Epstein-Barr Virus (EBV) seronegative participants; Epstein-Barr Virus (EBV) seropositive participants

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 (4)

• 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

• Miskovic R, Jeremic I, Miljanovic D, Cirkovic A, Banko A. How Epstein Barr virus shapes lupus autoimmunity: mechanistic insights and therapeutic perspectives. Front Immunol. 2026 Jun 2;17:1853891. doi: 10.3389/fimmu.2026.1853891. eCollection 2026.

  PMID: 42311676 DERIVED

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

Results Point of Contact

• Title: Durkee-Shock, Jessica
• Organization: National Institute of Allergy and Infectious Diseases

Jessica.durkee-shock@nih.gov

+1 301 761 6539

Study Officials

• Jessica R Durkee-Shock, M.D.

  National Institute of Allergy and Infectious Diseases (NIAID)

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• 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: April 1, 2026
• Last Updated: July 22, 2026
• Results First Posted: July 22, 2026

Record last verified: 2025-07

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR
• Time Frame: One year from publication of study result.
• Access Criteria: Data will be shared in de-identified format with other researchers on written request.

Locations

US (1)