This is an open-label, randomized, exploratory study to evaluate the human immune response to reduced subcutaneous (SQ) dosing of Yellow Fever vaccine compared to the standard FDA approved subcutaneous vaccination dose. The current dose of the US FDA licensed Yellow Fever vaccine is approximately 55,000 plaque-forming unit(s) (PFU) in 0.5 mL administered SQ. Using the licensed dosage as standard, investigators are evaluating reduced doses of 1/5th (0.10 mL) and 1/10th (0.05 mL) standard Yellow Fever vaccine (YF-VAX).

Up to 150 individuals will be screened in order to randomize 90 eligible individuals to one of three groups: Group 1- YF-VAX® standard dose 0.5 mL SQ = 30 subjects; Group 2-0.10 mL (1/5th) SQ = 30 subjects; Group 3-0.05 mL (1/10th) SQ = 30 subjects.

Inclusion Criteria:

1. Males and Females 18 to 50 years of age.
2. In good health, as determined by pertinent medical history, physical examination, vital signs, and clinical safety laboratory evaluations.
3. Female of child bearing potential: Has a negative pregnancy test and is willing to use a reliable form of contraception for the duration of the study after vaccination.
4. Negative human immunodeficiency virus (HIV) antibody screen, seronegative for hepatitis B surface antigen (HBsAg) and hepatitis C antibody (following HIV and hepatitis testing, subjects will be provided with counseling and referral for health care if any test is positive).
5. Ability to comprehend and a willingness to sign an informed consent, which includes the Health Insurance Portability and Accountability Act (HIPAA) Authorization, and a separate consent form for HIV testing.
6. Be willing to comply with all follow-up visits, testing, adverse event (AE) reporting, and completion of diary card.

Exclusion Criteria:

1. Receipt of any other investigational vaccine or investigational drug within 28 days prior to or after vaccination with YF-VAX® vaccine.
2. Have had any known flavivirus disease or receipt of any flavivirus vaccine, licensed or investigational at any time; in addition to any yellow fever vaccine, these include; Japanese Encephalitis (JE), St. Louis Encephalitis, Tick Borne Encephalitis (TBE), West Nile, Dengue, Zika virus
3. Anticipates receipt of any other vaccine within 28 days of YF-VAX®. Influenza vaccination will be permitted but not within 14 days of YF-VAX®.
4. Acute or chronic medical conditions, or medications that, in the Principal Investigator's (PI) opinion, would impair the subject's ability to respond to vaccination.
5. Hypersensitivity to any vaccine, eggs or egg products, or allergy to any component of the YF-VAX® (sorbitol, gelatin) or latex.
6. Corticosteroids ≥20 mg/day of prednisone for ≥ 2 weeks suppresses the immune system. Low-dose corticosteroid topical products and nasal sprays used sporadically (i.e. prn--according to circumstances) are permissible.
7. History of immunosuppression, by any cause--primary or acquired immunodeficiencies, transplantation, malignant neoplasm, lymphoma, leukemia, thymoma, myasthenia gravis, radiation, immunosuppressive drugs, including antimetabolites, tumor necrosis factor (TNF)-alpha inhibitors (etanercept), interleukin-1 (IL-1) blocking agents and other monoclonal antibodies targeting immune cells (e.g., rituximab, alemtuzumab, etc), etc.
8. Receipt of or anticipates receipt of/or donation of blood or blood products for 2 months after receipt of YF-VAX®. (Note: Blood banks require a minimum 2 week interval between the receipt of this FDA licensed vaccine and blood donations; however because of the blood collections in this study, an interval of 2 months is requested).
9. Female: Pregnant (or planning to become pregnant) or breastfeeding for the duration of the study after receipt of YF-VAX®.
10. Clinically significant abnormal laboratory tests (generally 2 times the upper limit of normal or as determined by the PI).

Analysis population included all subjects that signed consent & were randomized to a study group. Two targeted populations were defined for this study as outlined below. 1. Safety will be analyzed for all subjects who receive an injection of vaccine regardless of adherence to the protocol (intent to treat). 2. Subjects who receive vaccine & had titers drawn in compliance to protocol were included in the per protocol analysis set & used for immunogenicity and exploratory analysis (per protocol).

Adverse Events collected Up to one year following vaccination.

Solicited and non-Solicited adverse events collected.

This was a pilot study to establish proof of concept.