A Phase I/II Trial of a Tetravalent Live Attenuated Dengue Vaccine in Flavivirus Antibody Naïve Children

Inclusion Criteria

• A male or female child six to nine years of age (greater than or equal to 6 years of age and less than 10 years of age) at the time of the first vaccination.
• Free of obvious health problems as established by medical history and physical examination before entering into the study.
• Seronegative by HAI and screening PRNT for antibodies to dengue types 1-4 and Japanese Encephalitis (JE) virus
• Written informed consents by the parent of the subject for screening and enrollment into the study.

Exclusion Criteria

• Chronic administration (defined as more than 14 days) of immunosuppressants or other immune-modifying drugs within six months prior to the first vaccine dose or planned administration during the study (For corticosteroids, this will mean prednisone, or equivalent, greater than or equal to 0.5 mg/kg/day. Inhaled and topical steroids are allowed.)
• Use of any investigational or non-registered drug or vaccine other than the protocol-specified vaccines within 30 days preceding the administration of the first dengue vaccine dose or planned use during the study period.
• Planned administration of a vaccine not foreseen by the study protocol and within 30 days prior or after any dengue/JE vaccine administration.
• Any current medical condition determined to be serious by the investigator (e.g. seizures)
• History of chronic headaches or a first order family member (parent or sibling) with a history of chronic headaches
• Abnormal clinical laboratory screening test result (based on normal values set by the laboratory) that is deemed clinically significant by the investigator or Medical Monitor (including seropositivity for HBsAg or anti-HCV)
• Previous vaccination against yellow fever virus, JEV, or tick-borne encephalitis virus (TBE) or existence of any flavivirus antibody
• Any suspected or confirmed immunosuppressive or immunodeficient condition, including human immunodeficiency virus (HIV) infection
• Family history of a congenital or hereditary immunodeficiency
• Acute illness at time of enrollment (defined as the presence of a moderate or severe illness with or without fever). All vaccines can be administered to persons with a minor illness such as diarrhea or mild upper respiratory infection without fever, i.e., oral temperature <37.5°C.
• Administration of immunoglobulins and/or blood products within 6 months prior to study entry or planned administration during the study period
• History of allergic disease or reactions likely to be exacerbated by any component of the vaccines (including neomycin, streptomycin, gentamicin, amikacin, tobramycin, kanamycin and bacitracin; allergy to dogs or monkeys or hypersensitivity to proteins of rodent or neural origin or to thimerosal, allergy to porcine gelatin)
• Child whose parent has no easy access to a fixed or mobile telephone
• Plans to move from Bangkok during the first 8.5 months after initial vaccination
• Parental illiteracy.