A Controlled Human Infection Model of Dengue

Exclusion Criteria27

• Willing and able to commit to participation in the study.
• History or evidence of any clinically significant or currently active neurologic, cardiac, pulmonary, hepatic, rheumatologic, autoimmune, or renal disease.
• History of active depression and/or anxiety with associated severe psychiatric comorbidities, for example psychosis.
• 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.
• Significant history or presence of drug or alcohol misuse
• History of anaphylaxis and/or a history of severe allergic reaction or significant intolerance to any food or drug, as assessed by the PI.
• Family history of 1st degree relative aged 50 years or less with sudden cardiac or unexplained death
• A total body weight of ≤ 45kg and a Body Mass Index (BMI) ≤18 kg/m2 and ≥30 kg/m2.
• Venous access deemed inadequate for the phlebotomy demands of the study.
• 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.
• 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.
• 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.
• Medications:
• Receipt of any investigational drug within 3 months prior to the planned date of viral challenge
• Receipt of systemic (intravenous and/or oral) glucocorticoids or systemic antiviral drugs within 6 months prior to the planned date of viral challenge.
• 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).
• Participants who have received any systemic chemotherapy agent, immunoglobulins, or other cytotoxic or immunosuppressive drugs at any time.
• Participant is mentally or legally incapacitated in the opinion of the Investigator.
• Females who:
• Are breastfeeding within 6 months of study commencement, or
• Had been pregnant within 6 months prior to the study, or
• 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.
• Any other reason that the Investigator considered made the participant unsuitable to participate.
• 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.