Trial Evaluating the Immunogenicity and Safety of an Adjuvanted Epstein-Barr Virus (EBV) Glycoprotein 350 Vaccine in EBV-seronegative Persons

NCT05683834 | Completed Phase 1 FDA Drug

• 2 other identifiers: 10001048001048-I
• Study Type: interventional
• Target: 25
• Locations: 1 country
• Sites: 2

Brief Summary

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.

Conditions

Epstein-Barr Virus Infection; Herpesvirus; Infectious Mononucleosis

Keywords

Infectious Mononucleosis; Neutralizing Antibody; Immune Response; Herpesvirus

Outcome Measures

Primary Outcomes (1)

• Change in mean EBV neutralizing antibody from Day 0 to 30 days after the third dose of study vaccine in EBV gp350 Ferritin vaccine recipients as compared with placebo.

  To evaluate the safety and immunogenicity of the adjuvanted EBV gp350-Ferritin vaccine administered to healthy EBV-seronegative adults.

  Day 90-120

Secondary Outcomes (4)

• Reduction in EBV infection as measured by new anti-EBV VCA IgG or IgM or new EBV viremia for up to 2 years post-vaccination as compared with placebo

  Year 2

• Reduction of viremia measured by qPCR in EBV gp350 vaccine recipients as compared with placebo in participants who become infected with EBV

  End of Study

• Reduction EBV related infectious mononucleosis as defined by signs and symptoms consistent with infectious mononucleosis with laboratory evidence for new EBV infection for up to 2 years post-vaccination as compared with placebo

  Year 2

• Safety through day 90-120 Solicited local and systemic reactions within 7 days after study vaccine administration Unsolicited AEs through 30 days after the third dose of the study vaccine SAEs through 30 days after the th...

  Day 90-120

Study Arms (2)

Control

PLACEBO COMPARATOR

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.

Other: Placebo Comparator

Interventional

EXPERIMENTAL

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.

Drug: Matrix-M1 Adjuvant; Drug: EBV gp350-Ferritin Vaccine

Interventions

Matrix-M1 Adjuvant DRUG

Matrix-M1 is composed of 2 types of 40 nm-sized particles each with a different saponin fraction (fraction A and fraction B) combined with cholesterol and phospholipid.

Interventional

EBV gp350-Ferritin Vaccine DRUG

The EBV gp350-Ferritin vaccine is composed of Helicobacter pylori non-heme ferritin fused to EBV gp350 which self-assembles to form a nanoparticle. The vaccine is supplied in single-use vials at a concentration of 250 micrograms/mL in 1.7 mM KH2PO4, 5 mM Na2HPO4, 150 mM NaCl, 5% sucrose, pH 7.4 (diluent).

Interventional

Placebo Comparator OTHER

Normal Saline

Control

Eligibility Criteria

• Age: 18 Years - 25 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• To be eligible to participate in this study, an individual must meet all the following criteria:
• Aged 18 to 25 years.
• Able to provide informed consent.
• Willing to allow samples and data to be stored for future secondary research.
• Stated willingness to comply with all study procedures and availability for the duration of the active phase of the study (approximately 18 months).
• In good general health as evidenced by medical history, physical examination, and laboratory screening results.
• Willing to forgo receipt of a licensed, live vaccine in the 30 days before and 30 days after each dose of the study vaccine. Any FDA-approved or authorized inactivated and/or protein subunit, RNA, or DNA vaccine can be used \>=14 days before or \>=14 days after administration of the study vaccine.
• Hemoglobin within institutional normal limits, or if not, then assessed and deemed not clinically significant by PI or designee.
• White blood cell count and differential within institutional normal reference range, or if not, then deemed not clinically significant by PI or designee.
• Total lymphocyte count (lymphocyte absolute) \>800 cells/microliters.
• Platelet count of 125,000 to 500,000/microliters.
• Alanine aminotransferase \<1.25 x upper limit of normal.
• Participants who can get pregnant must agree to abstain from sexual activities that can result in pregnancy or use one of the following effective methods of contraception, starting 30 days before the first dose of study vaccine through 60 days after the third dose:
• 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 before the first dose of study agent). If the participant uses a contraceptive pill, patch, or ring, then a barrier method (eg, internal/external condom, cervical cap, or diaphragm plus spermicide) must also be used at the time of potentially reproductive sexual activity.

You may not qualify if:

• An individual who meets any of the following criteria will be excluded from participation in this study:
• Pregnant or breastfeeding, or planning to become pregnant while participating through 60 days after the third dose of study vaccine.
• Has received any of the following:
• More than 10 days of systemic glucocorticoids (\>=10 mg of prednisone or equivalent) within the 30 days prior to first dose of study agent.
• More than 10 days of systemic immunosuppressive medications, cytotoxic medications, or immunomodulating therapy within 180 days prior to first dose of study agent.
• Blood products, including immunoglobulins, within 120 days prior to first dose of study agent.
• Any live attenuated vaccination within 30 days prior to first dose of study agent.
• 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.
• Has any of the following:
• Febrile illness within 14 days of the first dose of study agent.
• 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 that required emergency 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 (2)

National Institutes of Health Clinical Center

Bethesda, Maryland, 20892, United States

Location

University of Minnesota

Minneapolis, Minnesota, 55455, United States

Location

Related Publications (3)

• 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

• 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

• 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

Related Links

• NIH Clinical Center Detailed Web Page

MeSH Terms

Conditions

Epstein-Barr Virus Infections; Infectious Mononucleosis; Herpes Simplex

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; Skin Diseases, Viral; Skin Diseases, Infectious; Skin Diseases; Skin and Connective Tissue 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: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 12, 2023
• First Posted: January 13, 2023
• Study Start: September 22, 2023
• Primary Completion: April 1, 2026
• Study Completion: April 20, 2026
• Last Updated: April 22, 2026

Record last verified: 2026-04-20

Data Sharing

• IPD Sharing: Will not share

Locations

US (2)