A Phase III clinical trial to evaluate the efficacy and safety of a single dose of “Dengue Vaccine (DengiAll)" in Healthy Indian Adults

INTERVENTION: Intervention1: Dengue Tetravalent Vaccine, Live Attenuated (Recombinant, Lyophilized) – DengiAll of Panacea Biotec Limited, India: A 0.5 ml of single dose of DengiAll will be administered subcutaneously over the non‐dominant arm. Control Intervention1: Placebo is a lyophilized powder to be reconstituted with diluent (sterile water for injection) before administration.: A 0.5 ml of single dose of Placebo will be administered subcutaneously over the nondominant arm CONDITION: PRIMARY OUTCOME: To evaluate the efficacy of “DengiAll ? among adults in preventing symptomatic laboratory confirmed dengue infection over a period of 2 years after vaccinationTimepoint: Febrile illness with laboratory confirmation of dengue determined by NS1‐ELISA and/or rRT‐PCR, occurring one month to 2 years post vaccination (vaccine or placebo). INCLUSION CRITERIA: 1. Healthy males and non‐pregnant females between 18 to 60 years of age, in good health, based on medical history, clinical laboratory tests (protocol specified), and physical examination. 2. Participants willing to participate throughout the study period of 2 years (after signing written informed consent) Inclusion Criteria for Women: ? Female with non‐childbearing potential (Females having documented history of surgical sterilization or are postmenopausal ‐ 12 months of amenorrhea after the last menstrual period) ? Female with childbearing potential is eligible if she: has used an effective method of contraception or abstinence from at least 4 weeks prior to vaccination AND is willing to avoid pregnancies up to 90 days post vaccination by use of an effective method of contraception or abstinence AND has negative serum pregnancy test on the screening day and negative urine p SECONDARY OUTCOME: 1.To determine the safety of “DengiAll ? in adults as assessed by the frequency of adverse events, graded by seriousness, causality and severity.Timepoint: 1a. All solicited AEs and Unsolicited AEs occurring within 28 days post vaccination, with respect to causality, seriousness, severity and frequency in ; reactogenicity cohort. ; ; 1b. SAEs throughout the study duration post vaccination, with respect to causality, ; severity and frequency among all participants. ; ; 1c. Related grade 3 and above unsolicited AEs through 28 days post‐vaccination with respect to severity and frequency in all participants. 2. To assess the immunogenicity of “DengiAll ? in comparison to the placebo using serum plaque reduction neutralization titer 50% (PRNT50) against dengue virus serotypes.Timepoint: 2a.The Geometric Mean Antibody serum plaque reduction neutralization titer 50 percent (PRNT50) to dengue virus serotypes in vaccinated and placebo arms on Days 0, 28, 56, 84 ,180, 1 year and 2 years post vaccination. ; ; 2b. Seroconversion and seropositivity rates by PRNT50 test to dengue virus serotypes on study days 28, 56, 84, 180, 1 year and 2 years post vaccination. ; ; 2c. Monovalent, bivalent, trivalent, and tetravalent seropositivity post vaccination. 3. To determine viremia in a subset of dengue naïve and exposed trial participants on Days 9 and Day 12 post vaccination.Timepoint: 3. Presence of Viremia for each serotype in a sub set of Dengue trial participants on Day 9 and Day 12 post vaccination. 4.To evaluate the efficacy of DengiAll among adults in preventing symptomatic laboratory confirmed dengue infection by dengue virus serotypes over a period of 2 years after vaccinationTimepoint: 4. Febrile illness with laboratory confirmed dengue occurring one month to 2 years post vaccination. 5. To compare the incidence of laboratory confirmed severe dengue and dengue related deaths between DengiAll and placebo groupsTimepoint: 5a. Incidence of Severe Dengue cases. ; ; 5b. Deaths among participants suffering from laboratory confirmed dengue and determined to be clinically related to dengue will be compared among vaccine and Placebo. 6. To evaluate the efficacy of DengiAll in preventing symptomatic laboratory confirmed dengue infection by baseline serostatus. ; Timepoint: 6. Febrile illness with laboratory confirmed dengue, occurring between one month and 2 years of vaccination, separately in baseline dengue seropositive and naïve individuals. 7. To assess the cell mediated immune responses post vaccination.Timepoint: 7a. The number of CD4, CD8 T cells and NK cells in whole blood of pre vaccination and post vaccination samples at Day 28, 180, 1 year and 2 years. ; ; 7b. T cell response for measurement of antigen specific cytokines and cytotoxic potential levels in PBMCs of pre vaccination and post vaccination samples at Day 28, 180, 1 year and 2 years. ; 8. Estimation of the ratio of Neutralizing Antibodies to Non Neutralizing Antibodies by NNT.Timepoint: 8. Ratio of the Neutralizing Antibodies to Non Neutralizing Antibodies by Net Neutralization Assay will be carried out on Day 28 and 84 in a subset of the immunogenicity cohort.