Optimal Human Dose for GII.2 Norovirus (Snow Mountain) Challenge Studies

Exclusion Criteria

• •1. Have household contact with or have daily contact with children under 2 years of age or persons older than 70 years of age
• •2. Have expected occupational or social contact with immunocompromised individuals in the 8 weeks after challenge, including persons with HIV infection or active cancer, children \<2 years of age, pregnant women or persons who are immunosuppressed (e.g. history of stem cell or organ transplantation). Individuals who provide any child day care services (in-home or non-residential facility) are also excluded
• •3. Are healthcare workers with patient contact in the 8 weeks after challenge
• •4. Are food service workers expected to prepare/handle food in the 8 weeks after challenge
• •5. Plan to be living in a confined environment (e.g. ship, camp, or dormitory) within 8 weeks after receiving the challenge strain
• •6. For females, are pregnant or plan to become pregnant at any time between the Screening Visit through 45 days after receipt of the challenge virus
• •7. Are breastfeeding or plan to breastfeed at any given time throughout the study
• •8. Have a history of gastroenteritis in the 4 weeks prior to challenge or any history of chronic or recurrent diarrhea or vomiting
• •9. Have a history of malabsorption or maldigestion disorder (e.g. celiac sprue), major gastrointestinal (GI) surgery, irritable bowel syndrome or any other chronic GI disorders that would interfere with the study, including chronic constipation or increased stool frequency
• •10. Have moderate or severe illness and/or an oral temperature \>/=100.4 degrees F and/or diarrhea or vomiting within seven days prior to challenge
• •11. Have a pulse rate less than 55 beats per minute (bpm) or greater than 100 bpm. If heart rate is \<55 bpm and the investigator determines that this is not clinically significant (e.g., athletes) and heart rate increases \> 55 bpm on moderate exercise (two flights of stairs), subject will not be excluded
• •12. Have a systolic blood pressure less than 90 mmHg or greater than 140 mmHg on two separate measurements (screening and pre-challenge)
• •13. Have a diastolic blood pressure less than 50 mmHg or greater than 90 mmHg on two separate measurements (screening and pre-challenge)
• •14. Have long-term use (\> /= 2 weeks) of high-dose oral (\>/= 20 mg per day prednisone or equivalent) or parenteral glucocorticoids, or high-dose inhaled steroids for greater than 7 days in the last 6 months
• •15. Have an autoimmune, inflammatory, vasculitic or rheumatic disease, including but not limited to systemic lupus erythematosus, polymyalgia rheumatic, rheumatoid arthritis or scleroderma
• •16. Have HIV, hepatitis B, hepatitis C infection or untreated latent syphilis
• •17. Have a seizure disorder
• •18. Have an active malignancy, history of malignancy (excluding nonmelanotic skin cancer in remission without treatment for more than 5 years) or current use of immunosuppressive or cytotoxic therapy
• •19. Have positive fecal culture for E. coli O157:H7, Salmonella, Campylobacter, Yersinia, or Shigella, evidence of norovirus in the stool by RT-qPCR or pathogenic ova and parasites detected on microscopic examination at screening
• •20. Have abnormal screening laboratory test results per laboratory reported normal values for white blood cells (WBCs), hemoglobin (Hgb), platelets, absolute neutrophil count (ANC), elevated total bilirubin, potassium, sodium and hemoglobin A1c (HbA1c) and urine protein
• •21. Have a serum creatinine greater than 1.1 x ULN
• •22. Have an ALT (SGPT) greater than 1.1 x ULN
• •23. Have a chronic condition that the study physician feels would pose a threat to participating subjects, including, but not limited to solid organ or stem cell transplantation, diabetes, clinically significant history of immunosuppressive illness, gall bladder disease, heart disease, lung disease, pancreatic disease, renal disease or neurological disease 24. Have abnormal findings on screening electrocardiogram deemed clinically significant by study physician
• •25\. Have ongoing drug abuse/dependence (including alcohol), or a history of these issues within 5 years of enrollment 26. Have a positive urine test for opiates 27. Have any medical, psychiatric, occupational, or behavioral problems that make it unlikely for the subject to comply with the protocol as determined by the investigator 28. Are unwilling to comply with study procedures including abstaining from smoking for the duration of the inpatient portion of the study 29. Have participated in a previous NoV challenge study or NoV vaccine study 30. Have received experimental products within 30 days before study entry or plan to receive experimental products at any time during the study 31. Plans to enroll in another clinical trial that could interfere with safety assessment of the investigational product at any time during the study period, including study interventions such as drugs, biologics or devices 32. Plan to donate blood during the course of the study 33. Have received a live vaccine within 30 days before study entry or plan to receive a live vaccine prior to Day 30 of the study 34. Have received an inactivated vaccine within 14 days before study entry or plan to receive an inactivated vaccine prior to Day 14 of the study 35. Have received parenteral immunoglobulin or blood products within 3 months of the study start, or plan to receive parenteral immunoglobulin or blood products within 3 months after receiving the study agent 36. Use of antibiotics within 7 days prior to entry into the inpatient facility 37. Use of any H2 receptor antagonists (e.g., Tagamet, Zantac, and Pepcid), proton pump inhibitors (e.g., Prilosec, Protonix, and Prevacid), or prescription acid suppression medication or over-the-counter (OTC) antacids in the 72 hours prior to NoV challenge 38. Use of prescription and OTC medications containing acetaminophen, aspirin, ibuprofen, and other non-steroidal anti-inflammatory drugs within 48 hours prior to NoV challenge 39. Regular use of laxatives or anti-motility agents 40. Have a history of allergy to sodium bicarbonate 40. Have a history of allergy to sodium bicarbonate