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.
Study Description: This is a phase 1 study to evaluate the safety of a 3-dose vaccination regimen of an adjuvanted 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 induce a potent immune response that neutralizes EBV infection of B cells and epithelial cells. There will be an initial dose escalation phase comprised of 9 EBV-seropositive individuals followed by a randomization phase comprised of 24 EBV-seropositive individuals and an additional 30 EBV-seronegative individuals. 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. Some individuals will receive only the EBV gH/gL/gp42-ferritin nanoparticle vaccine; others will receive EBV gH/gL/gp42-ferritin nanoparticle vaccine plus the gp350-ferritin nanoparticle vaccine. Participants will know which vaccine they have received during the study. Objectives: Primary objective: 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. Key secondary objective: To evaluate the immunogenicity of an adjuvanted EBV gH/gL/gp42-ferritin nanoparticle vaccine with or without gp350-ferritin nanoparticle in seronegative and seropositive healthy adults. Endpoints: Primary endpoints: * Local and systemic vaccine side effects during the 7-day period after each vaccination * All symptoms and diagnoses up to 30 days after each vaccination * Serious medical events (SAEs) through 30 days after the last dose of study vaccine. Key secondary endpoints: -Production of EBV neutralizing antibody after the vaccination series, as measured by B cell and epithelial cell neutralization assays.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
OTHER
Masking
NONE
Enrollment
750
The adjuvanted gH/gL/gp42-ferritin nanoparticle vaccine is given with gp350-ferritin intramuscularly into the deltoid muscle at 0, 1, and 4 months.
The adjuvanted gH/gL/gp42-ferritin nanoparticle vaccine is given with gp350-ferritin intramuscularly into the deltoid muscle at 0, 1, and 4 months.
National Institutes of Health Clinical Center
Bethesda, Maryland, United States
RECRUITINGLocal 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
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.
To evaluate the immunogenicity 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
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.
To further evaluate the immunogenicity of the adjuvanted EBV gH/gL/gp42-ferritin nanoparticle vaccine with or without gp350-ferritin.
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.
To determine whether the vaccine causes production of antibodies to H. pylori and/or human ferritin.
Time frame: Length of the study
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