safety and immunogenicity of various formulations of live attenuated tetravalent dengue vaccine in healthy us adults

Conditions: Dengue

Summary: this descriptive study will evaluate the safety and immunogenicity of 3 different formulations of the wrair dengue vaccine compared to a placebo.

subjects will be randomized into one of 4 groups. one group will receive a placebo vaccine and the others will receive one of 3 different dengue vaccine formations. each subject will receive two doses six months apart. study subjects who elect to participate in a mosquito transmissibility component of the study will undergo mosquito feedings during each of the two assigned follow-up visits after vaccine dose 1. all subjects will have 11 venipunctures during 11 visits (i.e., screening plus 10 study visits) over a period of nine months. a third (booster) dose of post transfection f17 or f19 will be administered approximately 5 to 12 months after dose 2 to all subjects who received one of these formulation for their first two doses. volunteers will return for a single visit 6 months after receiving their booster dose (long term follow-up)

Eligibility criteria:
inclusion criteria: * a healthy male or female adult 18-45 years at the time of vaccination; * free of obvious health problems as established by medical history and physical examination before entering into the study; * written informed consent obtained from the subject; * able to read the subject information sheet and consent form; * 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) should be enrolled in the study; * if the subject is female, she must be of non-childbearing potential, i.e. either surgically sterilized or one year post-menopausal; or, if of childbearing potential, she must be abstinent or have used adequate contraceptive precautions (i.e. intrauterine contraceptive device; oral contraceptives or other equivalent hormonal contraception, e.g. progestin implantable, cutaneous hormonal patch or injectable contraceptives) for 30 days prior to vaccination, have a negative pregnancy test within 48 hours prior to vaccination and must agree to continue such precautions for 60 days after completion of the vaccination series. exclusion criteria: * pregnant or lactating female; * female planning to become pregnant or planning to discontinue abstinence or contraceptive precautions; * history of any neurological or behavioral disorder or seizures, with the exception of a single febrile seizure in childhood; * history of drug abuse or alcohol consumption (more than 2 drinks per day); * history of allergic disease/reaction likely to be exacerbated by any component of the vaccine; * history of urticaria related to mosquito bites requiring medical attention; * acute or chronic, clinically significant pulmonary, cardiovascular, hepatic, renal, hematologic or endocrine functional defect, as determined by physical examination or laboratory tests; * any confirmed or suspected immunosuppressive or immunodeficient condition; * subject seropositive for hbsag, anti-hcv or anti-hiv; * acute disease at the time of enrollment (acute disease is defined as the presence of a moderate or severe illness with or without fever); * (vaccine can be administered to persons with a minor illness such as diarrhea, mild upper respiratory infection with or without low-grade febrile illness, i.e., oral temperature \<37.5°c/\<99.5°f.) * chronic hepatomegaly, right upper quadrant abdominal pain or tenderness; * chronic splenomegaly, left upper quadrant abdominal pain or tenderness; * use of any investigational or non-registered drug or vaccine other than the study vaccine within 30 days preceding the study vaccine (includes placebo) or planned use during the study period; * planned administration of a vaccine not foreseen by the study protocol during the period starting from 30 days before each dose of the study vaccine and ending 30 days after; * a planned move to a location that will prohibit participating in the trial for 9 months after the initial vaccination; * chronic administration (defined as more than 14 days) of immunosuppressants or other immune-modifying drugs within 90 days preceding the first dose or planned administration during the study period. for corticosteroids, this will mean prednisone, or equivalent, 0.5 mg/kg/day. inhaled and topical steroids are allowed; * administration of immunoglobulins and/or blood products within 90 days preceding the first dose or planned administration during the study period; * any chronic systemic drug therapy to be continued during the study period (except for vitamin/mineral supplements, a single anti-hypertension medication or routine treatment for gastro-esophageal reflux).