Evaluating the Safety and Immunogenicity of a Live Attenuated West Nile Virus Vaccine for West Nile Encephalitis in Adults 50 to 65 Years of Age

Inclusion Criteria: * Adult males and non-pregnant, non-breastfeeding females between 50 and 65 years of age, inclusive. Children will not be recruited or enrolled in this study for safety considerations. * Good general health, as determined by means of the screening procedures * Available for the duration of the trial * Willingness to participate in the study as evidenced by signing the informed consent form (ICF) Exclusion Criteria: * Pregnancy, as determined by positive beta-human choriogonadotropin (HCG) test (if female) * Currently lactating and breastfeeding (if female) * Participant is unwilling to use reliable contraception methods for the duration of the trial (reliable methods of birth control include: pharmacologic contraceptives including oral, parenteral, and transcutaneous delivery; condoms with spermicide; diaphragm with spermicide; surgical sterilization; intrauterine device; abstinence; and post-menopausal documented for at least 1 year). All female participants will be considered as having childbearing potential except for those with documented hysterectomy, tubal ligation, tubal coil (at least 3 months prior to vaccination), or who are post-menopausal for at least 1 year since last menstrual period. * Evidence of clinically significant neurologic, cardiac, pulmonary, hepatic, rheumatologic, autoimmune, or renal disease by history, physical examination, and/or laboratory studies * Behavioral, cognitive, or psychiatric disease that in the opinion of the investigator affects the ability of the participant to understand and cooperate with the study protocol * Screening laboratory values of Grade 1 or above for absolute neutrophil count (ANC), alanine aminotransferase (ALT), and serum creatinine, as defined in this protocol * Other condition that in the opinion of the investigator would jeopardize the safety or rights of a participant in the trial or would render the participant unable to comply with the protocol * Participant has had medical, occupational, or family problems as a result of alcohol or illicit drug use during the past 12 months * History of a severe allergic reaction or anaphylaxis * Severe asthma (emergency room visit or hospitalization within the last 6 months) * Positive HIV-1 serology by screening and confirmatory assays * Positive for hepatitis C virus (HCV) by screening and confirmatory assays * Hepatitis B virus (HBV) infection, by positive hepatitis B surface antigen (HBsAg) * Any confirmed or suspected immunosuppressive or immune modulating disorder (e.g., asplenia, lupus, rheumatoid arthritis, vasculitis, scleroderma, and diabetes mellitus) * Chronic administration (greater than or equal to 14 days) of steroids (defined as prednisone equivalent of greater than or equal to 10 mg per day), immunosuppressants, or other immune-modifying drugs initiated during the 28-day period post-vaccination (topical and nasal steroids are allowed) * Receipt of a live vaccine within 28 days or a killed vaccine within the 14 days prior to vaccination or anticipated receipt of any vaccine during the 28 days following vaccination * History of a surgical splenectomy * Receipt of blood products within the past 3 months, including transfusions or immunoglobulin, or anticipated receipt of any blood products or immunoglobulin during the 28 days following vaccination * History or serologic evidence of previous WNV infection or other flavivirus infection (e.g., yellow fever virus, St. Louis encephalitis virus, and dengue virus) * Previous receipt of yellow fever, WNV, or dengue vaccine (licensed or investigational) * Receipt of any investigational agent in the past 28 days or anticipation of receipt of any investigational agent within 28 days following vaccination * Refusal to allow storage of specimens for future research Inclusion Criteria for Second Dose: * Good general health, as determined by physical examination and review of medical history * Available for the duration of the study, approximately 26 weeks after the second dose * Ongoing willingness to participate in the study * Females only: female participants of childbearing potential willing to use effective contraception for the duration of the trial. Reliable methods of contraception include: hormonal birth control, condoms with spermicide, diaphragm with spermicide, surgical sterilization, intrauterine device, and abstinence (greater than 6 months since last sexual encounter). All female participants will be considered as having childbearing potential except for those with documented hysterectomy, tubal ligation, tubal coil (at least 3 months prior to vaccination), or who are post-menopausal for least 1 year since last menstrual period. Exclusion Criteria for Second Dose: * Anaphylaxis or angioedema following the first dose of vaccine * Females only: currently pregnant, as determined by positive beta-HCG test, or breastfeeding * Evidence of clinically significant neurologic, cardiac, pulmonary, hepatic, rheumatologic, autoimmune, or renal disease by history, physical examination, and/or laboratory studies * Behavioral, cognitive, or psychiatric disease that in the opinion of the investigator affects the ability of the participant to understand and cooperate with the requirements of the study protocol * Any other condition that in the opinion of the investigator would jeopardize the safety or rights of a participant in the trial or would render the participant unable to comply with the protocol * Any significant alcohol or drug abuse in the past 12 months that has caused medical, occupational, or family problems, as indicated by participant history * History of a severe allergic reaction or anaphylaxis * Severe asthma (emergency room visit or hospitalization within the last 6 months) * HIV infection, by screening and confirmatory assays * HCV infection, by screening and confirmatory assays * HBV infection, by HBsAg screening * Any confirmed or suspected immunosuppressive or immune modulating disorder (e.g., asplenia, lupus, rheumatoid arthritis, vasculitis, scleroderma, or diabetes mellitus) * Current use of anticoagulant medications * Chronic administration (greater than or equal to 14 days) of steroids (defined as prednisone equivalent of greater than or equal to 10 mg per day), immunosuppressants, or other immune-modifying drugs initiated during the 28-day period post-vaccination (topical and nasal steroids are allowed) * Receipt of a live vaccine within 28 days or a killed vaccine within the 14 days prior to vaccination or anticipated receipt of any vaccine during the 28 days following vaccination * History of surgical splenectomy * Receipt of blood products within the past 3 months, including transfusions or immunoglobulin or anticipated receipt of any blood products or immunoglobulin during the 28 days following vaccination * Receipt of any other investigational agent in the 28 days before vaccination or anticipated within 28 days following vaccination * Refusal to allow storage of specimens for future research