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