A Controlled Human Infection Model of Dengue

Inclusion Criteria: 1. An informed consent form (ICF) has been signed and dated by the participant, an investigator, and a witness 2. Adult, aged between 21 and 45 years, inclusive (at the time of consent) 3. No known history of prior dengue, zika or other Orthoflavivirus infection 4. No history of prior dengue, yellow fever, Japanese encephalitis virus, or other Orthoflavivirus vaccination 5. Sero-suitable based on the pre-screening serology result 6. a Female participants must be willing and able to use contraception from 2 weeks before the scheduled date of viral challenge until 1 month after receipt of the final dose of study virus. Negative urine pregnancy tests will be required at screening, and on admission to the quarantine unit a negative serum beta human chorionic gonadotropin (β-hCG) is required prior to inoculation. 6b Male participants who are willing to use one of the contraception methods described in the study protocol, from the date of viral challenge, for 1 month. In addition to the contraceptive requirements above, male participants must agree not to donate sperm following discharge from quarantine until 1 month after the date of viral challenge. 7 In good health with no history of clinically significant medical conditions (as described in Exclusion criteria) that would interfere with subject safety, as defined by medical history, physical examination and routine laboratory tests, ECG, and Chest X-Ray and determined by the Investigator at an admission evaluation. 8 Willing and able to commit to participation in the study. Exclusion Criteria: 1. History or evidence of any clinically significant or currently active neurologic, cardiac, pulmonary, hepatic, rheumatologic, autoimmune, or renal disease. 2. History of active depression and/or anxiety with associated severe psychiatric comorbidities, for example psychosis. 3. Behavioural, cognitive, or psychiatric disease that in the opinion of the investigator affects the ability of the subject to understand and cooperate with the requirements of the study protocol. 4. Significant history or presence of drug or alcohol misuse 5. History of anaphylaxis and/or a history of severe allergic reaction or significant intolerance to any food or drug, as assessed by the PI. 6. Family history of 1st degree relative aged 50 years or less with sudden cardiac or unexplained death 7. A total body weight of ≤ 45kg and a Body Mass Index (BMI) ≤18 kg/m2 and ≥30 kg/m2. 8. Venous access deemed inadequate for the phlebotomy demands of the study. 9. Any clinically significant abnormal finding on screening biochemistry, haematology and microbiology blood tests or urinalysis apart from minor deviations which are clinically acceptable and approved by the investigator. Any of the following: * Elevated HbA1C * Positive HIV, active/chronic hepatitis B or hepatitis C test. 10 Twelve-lead ECG recording with clinically relevant abnormalities as judged by the study investigator. 11 Receipt of a live vaccine within 60 days prior to the planned date of viral challenge, a non-live vaccine within 30 days prior to the planned date of viral challenge or intention to receive any vaccination(s) before the day 28 follow-up visit. 12 Previous receipt of a flavivirus vaccine (licensed or experimental). 13 Receipt of blood or blood products, or loss (including blood donations) of 550 mL or more of blood during the 3 months prior to the planned date of viral challenge or planned during the 3 months after the final visit. 14 Medications: 1. Receipt of any investigational drug within 3 months prior to the planned date of viral challenge 2. Receipt of systemic (intravenous and/or oral) glucocorticoids or systemic antiviral drugs within 6 months prior to the planned date of viral challenge. 3. Over the counter medications (e.g., paracetamol or ibuprofen) where the dose taken over the preceding 7 days prior to the planned date of viral challenge had exceeded the maximum permissible 24-hour dose (e.g., \>4g per day of paracetamol over the preceding week). 4. Participants who have received any systemic chemotherapy agent, immunoglobulins, or other cytotoxic or immunosuppressive drugs at any time. 15 Participant is mentally or legally incapacitated in the opinion of the Investigator. 16 Females who: 1. Are breastfeeding within 6 months of study commencement, or 2. Had been pregnant within 6 months prior to the study, or 3. Had a positive pregnancy test at any point during screening or prior to inoculation with challenge virus 17 Anyone who is first degree related to anyone who is a delegated member of the research team. 18 Any other reason that the Investigator considered made the participant unsuitable to participate. 19 Presence of symptoms and/or fever (defined as participant presenting with a temperature reading of \>37.9ºC) suggesting an infection at pre-challenge on Day 0.