Safety and Immunogenicity of an Epstein-Barr Virus (EBV) gp350-Ferritin Nanoparticle Vaccine in Healthy Adults With or Without EBV Infection

• INCLUSION CRITERIA:

In order to be eligible to participate in this study, an individual must meet all of the following criteria:

1. 18 to 29 years old

2. Screening procedures and evaluations performed no more than 30 days prior toscheduled administration of the first vaccine dose.

3. Ability of subject to understand and the willingness to sign a written informedconsent document.

4. Stated willingness to comply with all study procedures and availability for theduration of the active phase of the study (approximately 18 months)

5. Willingness to allow storage of blood and saliva for future research.

6. In good general health as evidenced by medical history, physical examination, andlaboratory screening result.

7. Subject is willing to forgo receipt of a licensed, live vaccine in the 30 dayspreceding each dose of vaccine or in the 30 days following each dose of vaccine. AnFDA-approved inactivated, subunit or replication-defective vaccine (such asCOVID-19, influenza, tetanus etc.) and/or a COVID-19 vaccine approved under emergency use authorizationcan be used >=14 days before or >=14 days after administration of the study vaccine.

8. 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 0and agreement to continue use until 60 days after the last dose of vaccine.

9. For males who are sexually active with partners of child-bearing potential: use ofhighly effective continuous contraception from Day 0 and agreement to continue useuntil 30 days after the last dose of vaccine. Contraceptive requirements: Because the effects of EBV gp350-Ferritin vaccine on thedeveloping human fetus are unknown, sexually active female participants ofchildbearing potential must agree to use highly effective contraception as outlinedbelow before study entry and until 60 days after the last dose of vaccine. Femalesof childbearing potential must have a negative pregnancy test before receiving eachdose of the EBV gp350-Ferritin vaccine. During the course of the study, if aparticipant becomes pregnant or suspects they are pregnant, then they should informthe study staff and their primary care physician immediately. Acceptable forms ofcontraception are:

• Intrauterine device (IUD) or equivalent

• Hormonal contraceptive (e.g. consistent, timely, and continuous use ofcontraceptive pill, patch, ring, implant, or injection that has reached fullefficacy 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 plusspermicide) must also be used at the time of potentially reproductive sexualactivity.

• A stable, long-term monogamous relationship with a partner who does not poseany potential pregnancy risk, e.g. has undergone a vasectomy at least 6 monthsprior to the first dose of vaccine or is of the same sex as the participant.

• A hysterectomy and/or a bilateral tubal ligation or bilateral oophorectomy Acceptable forms of contraception for male participants include one of thefollowing:

• Condom plus spermicide, used before or during sexual intercourse, even if thefemale partner uses a contraceptive pill, patch, or ring

• A vasectomy completed at least 6 months before the first dose of vaccine

• Continuously and completely abstaining from sexual intercourse with a femalewith child-bearing potential from the first dose of vaccine until 30 days afterthe last dose. Acceptable contraception for female partners with child-bearing potential of malestudy participants include one of the following:

• IUD or equivalent

• Hormonal contraceptive (e.g. pill, patch, ring, implant or an injection usedconsistently and that has reached full effect prior to the first dose ofvaccine)

• Hysterectomy and/or a bilateral tubal ligation or bilateral oophorectomy Laboratory Criteria within 30 days or less prior to enrollment:

10. Hemoglobin within institutional normal limits or if not, then assessed and deemednot clinically significant by PI or designee

11. White blood cell (WBC) count and differential either within institutional normalreference range or if not then assessed and deemed not clinically significant by PIor designee

12. Total lymphocyte count (lymphocyte absolute) >= 800 cells/mm3 (0.8 K/mcL)

13. Platelet count equal to 125,000 - 500,000/Mm^3 (125-500 K/mcL)

14. Alanine aminotransferase (ALT) <= 1.25x upper limit of normal (ULN)

15. Serum IgG > 600 mg/dL

16. Negative human immunodeficiency virus (HIV) test.

EXCLUSION CRITERIA:

An individual who meets any of the following criteria will be excluded from participation in this study:

1. Women who are breastfeeding or planning to become pregnant while participatingthrough 60 days after the last dose of vaccine

2. Participant has received any of the following:

• More than 10 days of systemic immunosuppressive medications (>=10 mg prednisonedose or its equivalent) or cytotoxic medication within the 30 days prior tofirst dose of vaccine or immunomodulating therapy within 180 days prior tofirst dose of vaccine.

• Blood products, including immunoglobulin products, within 120 days prior tofirst 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 planningto receive investigational products while on study

• Allergy treatment with antigen injections, unless on a maintenance schedule ofshots no more frequently than once per month.

3. 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 bestinterests of the participant

• Serious reactions to vaccines

• Hereditary, acquired, or idiopathic forms of angioedema

• Idiopathic urticaria within the past year

• Asthma that is not well-controlled or required emergent care, urgent care,hospitalization or intubation during the past 2 years or that requires the useof oral or intravenous steroids

• Diabetes mellitus type 1 or type 2, excluding a history of gestational diabetes

• Clinically significant autoimmune disease or immunodeficiency

• Hypertension that is not well-controlled

• Thyroid disease that is not well-controlled

• Bleeding disorder diagnosed by doctor (e.g. factor deficiency, coagulopathy, orplatelet disorder requiring special precautions)

• Significant bruising or bleeding difficulties with IM injections or blood draws

• Malignancy that is active or treated malignancy for which there is noreasonable assurance of sustained cure or malignancy that is likely to recurduring the study period

• Seizure disorder other than a history of 1) febrile seizures 2) seizuressecondary to alcohol withdrawal more than 3 years ago, or 3) seizures that havenot required treatment within the past 3 years

• Asplenia, functional asplenia or any condition resulting in absence or removalof the spleen.

• History of Guillain-Barre Syndrome

• Alcohol or drug abuse or addiction

4. Any medical, psychiatric, or social condition that, in the judgement of theinvestigator, is a contraindication to protocol participation or impairs theparticipant s ability to give informed consent.