Phase 1 Study of the Safety of an Epstein-Barr Virus (EBV) gH/gL/gp42-Ferritin Nanoparticle Vaccine With or Without gp350-Ferritin in Healthy Adults With or Without EBV Infection
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.
Detailed description
Study Description: This is a phase 1 study to evaluate the safety of a 3-dose vaccination regimen of an EBV gH/gL/gp42-ferritin nanoparticle vaccine with or without gp350-ferritin. Based on data reported in animal studies, our hypothesis is that this EBV vaccine will be safe. In addition, we hypothesize the vaccine will induce a potent immune response that neutralizes EBV infection of B cells and epithelial cells. In an initial dose escalation phase comprised of 9 EBV-seropositive individuals, 3 individuals will receive 50 micrograms adjuvanted gH/gL/gp42-ferritin vaccine alone, then 3 individuals will receive 25 micrograms adjuvanted gH/gL/gp42-ferritin vaccine + 25 micrograms gp350-ferritin vaccine, then 3 individuals will receive 50 micrograms adjuvanted gH/gL/gp42-ferritin vaccine + 50 micrograms gp350-ferritin vaccine. To distinguish reactogenicity and immunogenicity between the vaccine alone and the adjuvanted vaccine, we will include 3 individuals to receive gH/gL/gp42-ferritin vaccine alone without adjuvant,. This information will be used to select dosing of both vaccine and adjuvant for the randomization phase. Pending results of dose escalation, the study will progress to the randomization phase. Twenty-four EBV-seropositive individuals will be randomized in a 1:1 ratio to receive either 3 doses of 50 micrograms adjuvanted gH/gL/gp42-ferritin alone or 50 micrograms adjuvanted gH/gL/gp42-ferritin + gp350-ferritin nanoparticle. An additional 30 EBV-seronegative individuals will be randomized in a 1:1 ratio to receive either 3 doses of adjuvanted 50 gH/gL/gp42-ferritin alone or adjuvanted 50 micrograms gH/gL/gp42-ferritin + gp350-ferritin. Administration of gH/gL/gp42-ferritin with or without EBV gp350-ferritin will be performed open-label. If the combined dose of 50 micrograms adjuvanted gH/gL/gp42-ferritin vaccine + gp350-ferritin vaccine with or without adjuvant is not well tolerated during the dose escalation phase, the dosing of vaccine and/or adjuvant will be adjusted prior to starting the randomization phase. In each group, the vaccine will be given at 0, 1, and 4 months, and participants will be followed until at least 12 months after the third dose of vaccine with an option to be followed for an additional year. Objectives: Primary objective: To determine the safety of an EBV gH/gL/gp42-ferritin nanoparticle vaccine with or without gp350-ferritin nanoparticle in seronegative and seropositive healthy adults. Key secondary objective: To evaluate the immunogenicity via neutralization assay of an EBV gH/gL/gp42-ferritin nanoparticle vaccine with or without gp350-ferritin nanoparticle in seronegative and seropositive healthy adults. Other Secondary: To further evaluate the immunogenicity of the EBV gH/gL/gp42-ferritin nanoparticle vaccine with or without gp350-ferritin. To determine whether the vaccine causes production of antibodies to Helicobacter pylori and/or human ferritin. Endpoints: Primary endpoints: * Local and systemic reactogenicity signs and symptoms during the 7-day period after each vaccination * Unsolicited adverse events (AEs) up to 30 days after each vaccination * Serious adverse events (SAEs) through Day 150 Key secondary endpoints: * Change in log10 antibody response to EBV from baseline to 30 days after the third dose of vaccine (Day 150) as measured by the B-cell neutralization assay * Change in log10 antibody response to EBV from baseline to 30 days after the third dose of vaccine (Day 150) as measured by the epithelial cell neutralization assay Other secondary endpoints: * Change in log10 antibody response to EBV gp350, gp42, and gH/gL from baseline to Day 150 as measured by luciferase immunoprecipitation system (LIPS) assay * Enzyme-linked immunosorbent assay (ELISA)-determined dilution for antibodies to H. pylori and/or human ferritin on Day 0, Day 30, Day 60, and Day 150
Arms & interventions
- BiologicalEBV gp350-ferritin vaccine with ALFQ adjuvant
The adjuvanted gH/gL/gp42-ferritin nanoparticle vaccine is given with gp350-ferritin intramuscularly into the deltoid muscle at 0, 1, and 4 months.
- BiologicalEBV gH/gL/gp42-ferritin nanoparticle vaccine with ALFQ adjuvant
The adjuvanted gH/gL/gp42-ferritin nanoparticle vaccine is given with gp350-ferritin intramuscularly into the deltoid muscle at 0, 1, and 4 months.
Outcome measures
Primary
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.
Time frame: Through Day 150
Secondary
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.
Time frame: 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.
Time frame: 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.
Time frame: Length of the study
Eligibility criteria
Study locations (1)
National Institutes of Health Clinical Center
Bethesda, Maryland, 20892
References
- Cohen JI. Epstein-barr virus vaccines. Clin Transl Immunology. 2015 Jan 23;4(1):e32. doi: 10.1038/cti.2014.27. eCollection 2015 Jan.(PubMed)
- 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.(PubMed)
- 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.(PubMed)