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:

1. Age 18-45 at the time of consent

2. Ability and willingness to sign informed consent

3. Passing score on comprehension test of at least 75%, with up to 3 attempts

4. Available for the study period

5. Willing to use contraception for the duration of the study

6. Provide consent for release of medical history records from primary care physician,
college or university, urgent care or emergency room visit

Exclusion Criteria:

1. Female: pregnant or lactating

2. 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.

3. Female subjects using an intrauterine device (IUD) or Mirena®

4. Female subjects with fibroids or uterine polyps, endometriosis, adenomyosis, and
uterine scarring (e.g., after D&C)

5. 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.

6. Active Diabetes or active peptic ulcer disease (PUD)

7. Chronic obstructive pulmonary disease (COPD) or coronary artery disease (CAD)

8. 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)

9. Current, or a history of, auto-immune disease

10. History of Guillain-Barré syndrome (GBS)

11. Any history of FV infection or FV vaccination; or planned FV vaccination, outside the
study protocol, during the study period

12. 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.

13. Planned travel during the study period (180 days) which would interfere with the
ability to complete all study visits

14. 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

15. 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

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

17. Significant screening physical examination abnormalities at the discretion of the
investigator

18. Women who intend to become pregnant or men who intend to father a child during the
study period (approximately 180 days)

19. 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

20. Planning to donate blood in the 1 year following inoculation with dengue

21. Recent blood donation within prior 56 days of inoculation

22. Receipt of blood products or antibodies within 56 days of inoculation or during the
study period

23. 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

24. Recent or scheduled receipt of any vaccine 4 weeks prior to or after virus inoculation

25. Beliefs that bar the administration of blood products or transfusions

26. Positive urine screen for cocaine, amphetamines, or opiates

27. Currently taking Methadone or Suboxone

28. Currently taking anti-coagulant medication, aspirin or non-steroidal anti-inflammatory
drugs (NSAIDs)

29. 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

30. Chronic medical condition that, in the opinion of the investigator, impacts subject
safety.