Expansion of a Dengue-1 Live Virus Human Challenge

This is an expansion of a previous study conducted under NCT02372175. In this study up to nine healthy subjects between 18 and 45 years old will be inoculated with Dengue 1 Live Virus Human Challenge (DENV-1-LVHC) at a dose used in the previous study. Subjects will be closely monitored for the first 28 days with continued follow up through 6 months. Clinical and laboratory parameters, viremia and antibody levels will be assess. The goal is to expand the data set of symptoms produced by uncomplicated dengue-like illness.

Inclusion criteria

• Age 18-45 at the time of consent
• Ability and willingness to sign informed consent
• Passing score on comprehension test of at least 75%, with up to 3 attempts
• Available for the study period
• Willing to use contraception for the duration of the study
• Provide consent for release of medical history records from primary care physician, college or university, urgent care or emergency room visit

Exclusion criteria

• Female: pregnant or lactating
• Heavy menstrual bleeding within the last 6 months- menstrual periods lasting longer than 6 days, or requiring 5 or more pads or tampons per day.
• Female subjects using an intrauterine device (IUD) or Mirena®
• Female subjects with fibroids or uterine polyps, endometriosis, adenomyosis, and uterine scarring (e.g., after D&C)
• Blood tests confirming infection with human immunodeficiency virus- 1 (HIV-1), hepatitis C, hepatitis B (assessed by HbsAg) virus, or positive antibodies to the flaviviruses (FV) dengue, West Nile, Yellow Fever, Japanese encephalitis, or Zika.
• Active Diabetes or active peptic ulcer disease (PUD)
• Chronic obstructive pulmonary disease (COPD) or coronary artery disease (CAD)
• Known or suspected congenital or acquired immunodeficiency; or receipt of immunomodulation therapy such as anti-cancer chemotherapy or radiation therapy; or long-term systemic corticosteroid therapy (prednisone or equivalent for more than 2 consecutive weeks within the past 3 months)
• Current, or a history of, auto-immune disease
• History of Guillain-Barré syndrome (GBS)
• Any history of FV infection or FV vaccination; or planned FV vaccination, outside the study protocol, during the study period
• Diagnosis with Bipolar Disorder or Schizophrenia, hospitalization in the past year for a mental health disorder, or any other psychiatric condition, which in the opinion of the investigator prevents the subject from participating in the study.
• Planned travel during the study period (180 days) which would interfere with the ability to complete all study visits
• Recent (in the past 4 weeks) travel to any dengue endemic area. These potential subjects may be eligible for enrollment a minimum of 4 weeks later
• Any grade 2 laboratory abnormalities prior to inoculation for the tests specified in Table 18 and Table 19 of the protocol, except those listed in exclusion criteria 16
• Subjects with the following grade 1 or greater lab abnormalities: Creatinine; Liver Function Tests - ALT, AST; Hemoglobin (females and males); White Blood Cell (WBC) decrease; Platelets decreased; Prothrombin Time (PT); Partial Thromboplastin Time (PTT); Fibrinogen decrease
• Significant screening physical examination abnormalities at the discretion of the investigator
• Women who intend to become pregnant or men who intend to father a child during the study period (approximately 180 days)
• Hives, shortness of breath, swelling of the lips or throat, or hospitalization related to a previous vaccination or an allergy to specific medications/animals for which antigens may be in the virus preparations to include: shellfish allergy, fetal bovine serum, L-glutamine, neomycin and streptomycin
• Planning to donate blood in the 1 year following inoculation with dengue
• Recent blood donation within prior 56 days of inoculation
• Receipt of blood products or antibodies within 56 days of inoculation or during the study period
• Participation (active or follow-up phase) or planned participation in another vaccine, drug, medical device, or medical procedure clinical trial in the 4 weeks prior to this trial, during the trial, or 6 months following inoculation in this clinical trial
• Recent or scheduled receipt of any vaccine 4 weeks prior to or after virus inoculation
• Beliefs that bar the administration of blood products or transfusions
• Positive urine screen for cocaine, amphetamines, or opiates
• Currently taking Methadone or Suboxone
• Currently taking anti-coagulant medication, aspirin or non-steroidal anti-inflammatory drugs (NSAIDs)
• Chronic migraine headaches, defined as more than 15 headache days per month over a 3 month period of which more than 8 are migraines, in the absence of medication over use
• Chronic medical condition that, in the opinion of the investigator, impacts subject safety.