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)
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
PREVENTION
Masking
QUADRUPLE
Enrollment
86
Dengue tetravalent Vaccine F17 Pre transfection: 0.5 mL volume per dose, administered at 0 and 6 months via subcutaneous injection
Dengue tetravalent Vaccine F17 Post transfection: 0.5 mL volume per dose, administered at 0 and 6 months via subcutaneous injection. For the booster phase of the study, a booster dose was administered at five months to one year following the second dose.
Dengue tetravalent Vaccine F19 Post transfection: 0.5 mL volume per dose, administered at 0 and 6 months via subcutaneous injection. For the booster phase of the study, a booster dose was administered at five months to one year following the second dose.
Walter Reed Army Institute of Research
Silver Spring, Maryland, United States
N Antibody, Geometric Mean Titer(GMT) to Dengue Serotypes 1, 2, 3 and 4
GMTs for DEN neut. antibodies -unprimed subjects (primary and booster ATP Cohort for immunogenicity) PRE = Pre dose PI(M1) = Post dose 1, month 1 PII(M7) = Post dose 2, month 7 PRE III = Pre dose 3 PIII(M1) = Post dose 3, month 1
Time frame: Pre dose 1, 1 month post dose 1, 7 months post dose 2, Pre dose 3 and 1 month post dose 3
Percentage of Subjects Seropositive for Dengue Serotypes 1, 2, 3 and 4
Serpositivity rates for DEN neut. antibodies -unprimed subjects (primary and booster ATP Cohort for immunogenicity) PRE = Pre dose PI(M1) = Post dose 1, month 1 PII(M7) = Post dose 2, month 7 PRE III = Pre dose 3 PIII(M1) = Post dose 3, month 1
Time frame: Pre dose 1, 1 month post dose 1, 7 months post dose 2, Pre dose 3 and 1 month post dose 3
Occurrence of Any, and Grade 3 Solicited Adverse Events (AEs) Within 21 Days Follow-up After Dose 1 of Study Vaccine
Diary cards, digital thermometers, and small rulers were provided to subjects to record local and general solicited symptoms(pain, redness and swelling at the injection site, fatigue, headache, pain behind the eyes, abdominal pain, nausea, vomiting, muscle aches, joint aches, rash, photophobia and pruritis) and oral temperature taken daily for 21 days (days 0 through 20). The observations were to be recorded each evening and account for the previous 24 hours. If multiple temperature measurements were taken throughout the day, the maximum temperature was to be recorded.
Time frame: 21 days following 1st vaccination dose
Occurrence of Any, and Grade 3 Solicited Adverse Events (AEs) Within 21 Days Follow-up After Dose 2 of Study Vaccine;
Time frame: within 21 days after vaccination
Unsolicited Adverse Events Within 31 Days After Each Dose of Study Vaccine Dose
Summary of Unsolicited Adverse Events within 31 days after each dose of study vaccine dose (Primary total vaccinated cohort)
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Sterile solution of buffered water (0.9% NaCl), U.S. FDA accepted vaccine excipient, phenol red dye(phenolsulfonphthalein, used in vaccines as a pH indicator); 0.5 mL volume per dose, administered at 0 and 6 months via subcutaneous injection
Time frame: within 31 days of study vaccine
Occurrence of Serious Adverse Events (SAEs) Throughout the Entire Study Period.
Serious adverse events will be recorded throughout the entire study period. Subjects instructed to contact the investigator immediately should they manifest any signs or symptoms they perceive as serious. An identification card and a set of phone numbers to contact study staff 24 hours a day, 7 days a week given to subjects.
Time frame: Days 0 to 270
Occurrence of Abnormal Findings at Physical Examination After Each Vaccine Dose
Abnormal findings at DEN physical examination were defined as: rash, generalized rash, hemorrhages (skin, conjunctival or mucosal), conjunctival injection, hepatomegaly, splenomegaly or lymphadenopathy; generalized lymphadenopathy (palpable lymph nodes in 4 or more of the following locations: cervical, axillary, inguinal or other with right and left sides considered as separate locations) positive tourniquet test (WHO criterion of 20 or more petechiae per 2.5 cm square)Results were reported positive/negative using the WHO criterion.
Time frame: throughout the 202 day study
Percentage of Subjects With Suspected and Confirmed Dengue Reported During the 31-day Post-vaccination Period (Total Vaccinated Cohort)
The case definition of confirmed dengue used in this protocol requires fever (equivalent to an oral temperature ≥38.0ºC/≥ 100.4ºF) for three or more successive days, at least two of the signs or symptoms consistent with "suspected dengue" occurring during the period of fever, at least one clinical laboratory abnormality, and DEN viremia detected by RTqPCR. Cases not meeting all criteria were not considered "confirmed dengue." The percentage of subjects with suspected or confirmed dengue were tabulated by group after each vaccination.
Time frame: Days 0-30 post vaccination periods (total vaccinated cohort)
Neutralizing Antibody Sero-response to Each Dengue Serotype After Each Dose
Sero-response defined as: For initially seronegative(S-) subjects, antibody titer \>=10 DE50 at PI(M1) For initially seropositive(S+) subjects, antibody titer at PI(M1) \>=4 fold the pre-vacciniation neut. antibody titer
Time frame: Days 0 to 270
Neutralizing Antibody Sero-response to Each Dengue Serotype After Each Dose (Continued)
Sero-response defined as: For initially seronegative(S-) subjects, antibody titer \>=10 DE50 at PI(M1) For initially seropositive(S+) subjects, antibody titer at PI(M1) \>=4 fold the pre-vacciniation neut. antibody titer
Time frame: Days 0 to 270
Occurrence of Measurable Dengue Viremia at Specified Time Points Following Each Vaccine Dose.
For vireimia: Negative = GEQ/µl result is equal to zero Undetermined = GEQ/µL result is below LOD Positive = GEQ/µL result is \>= LOD
Time frame: Days 0 to 270