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.
Study Description: Phase 1 study to evaluate the safety and immunogenicity of a 3-dose vaccination regimen of an adjuvanted EBV gp350-Ferritin nanoparticle vaccine. Based on data reported in animal studies, our hypothesis is that this EBV vaccine will be safe and will induce a potent EBVgp350-specific immune response. Twenty EBV seropositive participants and 20 EBV seronegative participants will receive 3 doses of vaccine at 0, 1, and 6 months. Subjects will be followed until 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 and immunogenicity of an adjuvanted EBV gp350- Ferritin vaccine administered as three (3) intramuscular injections to healthy adults with or without prior EBV infection. Secondary objective: To further evaluate the immunogenicity of an adjuvanted EBV gp350-Ferritin vaccine administered to healthy adults. Endpoints: Primary endpoint consists of: * Local and systemic reactogenicity signs and symptoms during the 7-day period after each vaccination * Unsolicited adverse events up to 30 days after each vaccination * Serious adverse events through Day 210 * Change in log10 antibody response to EBV from baseline to 1 month after the third dose of vaccine (Day 210) as measured by neutralization assay Secondary endpoints: * Change in log10 antibody response to EBV gp350 from baseline to Day 210 as measured by luciferase immunoprecipitation system (LIPS) assay * Change in log10 CD4 T cell response to EBV gp350 from baseline to Day 210 as measured by intracellular cytokine staining
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
OTHER
Masking
NONE
Enrollment
83
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..
National Institutes of Health Clinical Center
Bethesda, Maryland, United States
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.
Time frame: 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
Time frame: 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.
Time frame: 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
Time frame: 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
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: Day 0 and Day 210
Change in Antibody Responses to EBV gp350; Change in CD4+ T Cell Responses to EBV gp350
-Change in log10 antibody response to EBV from baseline to 1 month after third vaccine dose measured by a luciferase immunoprecipitation assay; --Change in log10 CD4+ T cell response from baseline to one month after third dose measured by an intracellular cytokine staining assay.
Time frame: Change in antibody responses and change in CD4 T cell responses at 1 month after third dose of vaccine
This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.