Study of Varying Injection Schedules of TDENV-PIV Vaccine With AS03B Adjuvant and Placebo in Healthy US Adults

Inclusion criteria

• Subjects must be able to provide written informed consent.
• Subjects must be healthy as established by medical history and clinical examination at study entry
• Subjects who the investigator believes can and will comply with the requirements of the protocol (e.g., completion of the diary cards, return for follow-up visits, etc.)
• Subjects at WRAIR CTC must be able to pass Department of Defense (DoD) base entry requirements, including the possession of a valid government issued ID card.
• Male or non-pregnant, non-breastfeeding female between 20 and 49 years of age (inclusive) at the time of consent
• Female subjects of non-childbearing potential (non-childbearing potential is defined as having had one of the following: a tubal ligation at least 3 months prior to enrollment, a hysterectomy, an ovariectomy, or is post-menopausal).
• Female subjects of childbearing potential may be enrolled in the study, if all of the following apply:

• Practiced adequate contraception (see Definition of Terms, section 5) for 30 days prior to vaccination
• Has a negative urine pregnancy test on the day of vaccination
• Agrees to continue adequate contraception until two months after completion of the vaccination series.

Exclusion criteria

• Use of any investigational or non-registered product (drug or vaccine) other than the study vaccines/placebo during the period starting 30 days preceding the first dose of study vaccine/placebo and/or planned use during the study period
• Chronic administration (defined as more than 14 days in total) of immunosuppressants or other immune-modifying drugs during the period starting 90 days prior to the first vaccine/placebo dose (for corticosteroids, this will mean prednisone >=5mg/day or equivalent; inhaled, intranasal and topical steroids are allowed)
• Planned administration or administration of a vaccine/product not planned in the study protocol during the period starting 30 days prior to the first dose of vaccine/placebo until 30 days after the last dose of study vaccine/placebo (routine influenza vaccination will be allowed as long as it is not administered within 14 days of the vaccine/placebo, and will not lead to study exclusion although it should be reported to the PI)
• History of dengue infection or dengue illness, or history of flavivirus vaccination (e.g., yellow fever, tick-borne-encephalitis virus [TBEV], Japanese encephalitis, and dengue)
• Planned administration of any flavivirus vaccine for the entire study duration
• Concurrently participating in another clinical study, at any time during the study period, in which the subject has been or will be exposed to an investigational or a non-investigational product (pharmaceutical product or device)
• Any confirmed or suspected immunosuppressive or immunodeficient condition, based on medical history and physical examination (no laboratory testing required)
• Family history of congenital or hereditary immunodeficiency
• Autoimmune disease or history of autoimmune disease
• History of any reaction or hypersensitivity likely to be exacerbated by any component of the study vaccine/placebo or related to a study procedure
• Major congenital defects or serious chronic illness
• History of any neurological disorders or seizures
• Diagnosed with excessive daytime sleepiness (unintended sleep episodes during the day present almost daily for at least 1 month) or narcolepsy; or history of narcolepsy in a subject's parent, sibling, or child
• Acute disease and/or fever (≥37.5°C/99.5°F oral body temperature) at the time of enrollment: note that a subject with a minor illness such as mild diarrhea, mild upper respiratory infection, etc., without fever, may be enrolled at the discretion of the investigator
• Acute or chronic, clinically significant pulmonary, cardiovascular, hepatic or renal functional abnormality, as determined by physical examination or laboratory screening tests
• Administration of immunoglobulins and/or any blood products during the period starting 90 days preceding the first dose of study vaccine/placebo or planned administration during the study period
• Recent history of chronic alcohol consumption (more than 2 drinks per day and/or drug abuse (based on subject reported history)
• Pregnant or breastfeeding female or female currently planning to become pregnant or planning to discontinue adequate contraception
• A planned move to a location that will prohibit participating in the trial until Study End for the participant
• Any other condition which, in the opinion of the investigator, prevents the subject from participating in the study.
• Subject seropositive for hepatitis B surface antigen (HBsAg), hepatitis C virus antibodies (anti-HCV), or human immunodeficiency virus antibodies (anti-HIV)
• Safety laboratory test results at screening that are deemed clinically significant or more than Grade 1 deviation from normal