Trial to Model Primary, Secondary, and Tertiary Dengue Using a Monovalent Vaccine

INCLUSION CRITERIA: To be eligible to participate in this study, an individual must meet all the following criteria: Aged 18 to 59 years. In good general health as evidenced by medical history, physical examination, and laboratory screening results. Willing to allow storage of samples and data for future research. Willing to forgo receipt of any vaccine in the 28 days preceding the vaccine or in the 28 days following the dose of vaccine. For participants opting for LN FNA on day 57, they must be willing to forgo any vaccine through final LN FNA. For individuals who can become pregnant: use of at least one method of highly effective contraception from the invitation to participate in the trial through day 28 after vaccination. Able to provide informed consent. Willing to adhere to lifestyle considerations for the duration of the study. Willing to avoid travel to a dengue-endemic area as defined by the Centers for Disease Control and Prevention (CDC) for the duration of their participation in the study. Absolute neutrophil count (ANC) > 750 cells/microliter. Creatinine < 1.5 mg/dL. ALT < 1.25 x upper limit of normal. Serologic evidence of previous dengue virus infection indicative of either one previous DENV1, 2, or 4 infection or infection with at least two different serotypes. --For the flavivirus-na(SqrRoot) ve group, they must have no history of flavivirus vaccination, medical illness concerning for a flavivirus infection, or travel history that increases the likelihood of other flavivirus infections. If there is uncertainty about a previous flavivirus exposure, then confirmatory antibody testing against the virus of interest must be negative. Agree to avoid participation in other clinical studies requiring investigational interventions for the duration of this study (180 days). Agree to avoid blood and plasma donation outside this study through day 28. Contraceptive requirements: Participants who can get pregnant must agree to use highly effective contraception as outlined below from the invitation to participate in the study (approximately 2 weeks after screening) through day 28. Day 0 will be scheduled at least 28 days after the initiation of effective contraception. Participants who can get pregnant must have a negative pregnancy test on day 0 before receiving rDEN3DELTA30/31-7164. If a participant becomes pregnant or suspects they are pregnant by day 28, then they should inform the study staff and their primary care physician immediately. Acceptable forms of contraception are: Intrauterine device or equivalent. Hormonal contraceptive (eg, consistent, timely, and continuous use of contraceptive pill, patch, ring, implant, or injection that has reached full efficacy prior to dosing). Condom, diaphragm, or cervical cap plus spermicide. A stable, long-term monogamous relationship with a partner who does not pose any potential pregnancy risk, eg, has undergone a vasectomy at least 6 months prior to vaccination or is of the same sex as the participant. A hysterectomy and/or a bilateral tubal ligation, bilateral oophorectomy, or post-menopausal status defined as age >=45 years and at least 1 year since last menstrual period. Pregnancy after day 28 will not be exclusionary as this will not impact our primary endpoints, which are all within the first 28 days. Additionally, pregnancy is unlikely to impact our secondary endpoints, since it is not known to alter antibody neutralization. Although we may observe pregnancy-associated differences in the transcriptome, these endpoints are exploratory and we have chosen to prioritize safety and inclusivity for people who can become pregnant. Study blood draw volumes after day 28 are less than the recommended volumes for research blood in critically ill patients. Pregnant participants will be excluded from LN FNA due to the potential risks of anesthetics that may be used. Pregnancy testing will be performed on each LN FNA day, with a negative result required to proceed to aspiration. EXCLUSION CRITERIA: An individual who meets any of the following criteria will be excluded from participation in this study: Pregnant at screening. History of or positive test result for HIV, hepatitis B, or hepatitis C. History of previous dengue vaccine. Has any of the following: More than 10 days of systemic immunosuppressive medications (>=10 mg prednisone dose or its equivalent) or cytotoxic medication within the 30 days prior to vaccination or immunomodulating therapy within 180 days prior to vaccination. Received blood products, including immunoglobulin products, within 120 days prior to vaccination. History of serious reactions to vaccines. Hereditary, acquired, or idiopathic forms of angioedema. Idiopathic urticaria within the past year. Asthma that is not well controlled or required emergency care, urgent care, hospitalization, or intubation during the past two years or that requires the use of oral or intravenous steroids. Type 1 or type 2 diabetes mellitus that is not well controlled (hemoglobin A1c > 8). Clinically significant autoimmune disease or immunodeficiency. Blood pressure >= 180/110 (stage 3 hypertension) on at least 2 measures. Documented diagnosis of a bleeding disorder (eg, factor deficiency, coagulopathy, or platelet disorder requiring special precautions). Significant bruising or bleeding difficulties with subcutaneous injections or blood draws. Malignancy that is active or treated malignancy for which there is no reasonable assurance of sustained cure, or malignancy that is likely to recur during the study period. Asplenia or functional asplenia. Current alcohol or drug abuse or addiction and/or positive drug screen with substances other than marijuana. Any medical, psychiatric, or social condition that, in the judgement of the investigator, is a contraindication to protocol participation.