Low Pathogenicity Avian H10N7 Influenza Virus in a Healthy Human Challenge Model

This is an interventional basic science trial for Influenza Infection focused on measuring Influenza A, H10N7, Challenge Model, Influenza, Human Challenge Read More

• INCLUSION CRITERIA:

An individual must meet all of the following criteria to be eligible for study participation:

1. Greater than or equal to 18 and less than or equal to 50 years of age.
2. Able to provide consent.
3. Agrees to not use tobacco products, marijuana, or vaping products during participation in this study.
4. Willing to remain in isolation for a minimum of 10 calendar days (or for the duration of viral shedding) and to comply with all study requirements.

5. A male subject is eligible for the study if he meets one of the following criteria, beginning at least 4 weeks prior to enrollment and continuing until 10 weeks after administration of the human challenge virus and follow-up visit #4:

   1. Is infertile, including history of successful vasectomy.
   2. Agrees to practice abstinence.
   3. Agrees that, with heterosexual intercourse with a fertile female partner, he will use a condom with spermicide and his female partner (including those who have undergone bilateral tubal ligation) will use an acceptable form of contraception (see inclusion criterion 6c).

6. A female participant is eligible for this study if she is not pregnant or breastfeeding and meets one of the following criteria, beginning at least 4 weeks prior to enrollment and continuing until 10 weeks after administration of the human challenge virus and follow-up visit #4:

   1. Is infertile, including postmenopausal status (as defined by no menses for greater than or equal to 1 year) or history of hysterectomy.
   2. Agrees to practice abstinence.
   3. Agrees that, with heterosexual intercourse with a fertile male partner, she will use an acceptable form of contraception and her male partner will use a condom with spermicide. Acceptable effective methods of female contraception include the following: bilateral tubal ligation, implant of levonorgestrel, injectable progestogen, intrauterine device, oral contraceptive pills, and diaphragm with spermicide.
7. Willing to have samples stored for future research.
8. Human immunodeficiency virus (HIV) uninfected with a negative test within 60 days of inoculation (Day 0).

EXCLUSION CRITERIA:

An individual meeting any of the following criteria will be excluded from study participation:

1. Has self-reported or medically documented significant medical condition including but not limited to:

   1. Chronic pulmonary disease (e.g., asthma, emphysema).
   2. Chronic cardiovascular disease (e.g., cardiomyopathy, congestive heart failure, cardiac surgery, ischemic heart disease, known anatomic defects).
   3. Chronic medical conditions requiring close medical follow-up or hospitalization during the past 5 years (e.g., insulin-dependent diabetes mellitus, renal dysfunction, hemoglobinopathies).
   4. Immunosuppression or ongoing malignancy.
   5. Neurological and neurodevelopmental conditions (e.g., cerebral palsy, epilepsy, stroke, seizures).
   6. Post-infectious or post-vaccine neurological sequelae.

2. Has close or household (i.e., share the same apartment or house) high-risk contacts including but not limited to:

   1. Persons greater than or equal to 65 years of age.
   2. Children less than or equal to 5 years of age.
   3. Residents of nursing homes.

   4. Persons of any age with significant chronic medical conditions such as:

      • Chronic pulmonary disease (e.g., asthma).
      • Chronic cardiovascular disease (e.g., cardiomyopathy, congestive heart failure, cardiac surgery, ischemic heart disease, known anatomic defects).
      • Chronic medical conditions requiring medical follow-up or hospitalization during the past 5 years (e.g., insulin-dependent diabetes mellitus, renal dysfunction, hemoglobinopathies).
      • Immunosuppression or cancer.
      • Neurological and neurodevelopmental conditions (e.g., cerebral palsy, epilepsy, stroke, seizures).
      • Persons who are receiving long-term aspirin therapy.
      • Women who are pregnant, trying to become pregnant, or breastfeeding.
3. Has a body mass index (BMI) less than or equal to 18.5 or greater than or equal to 35.
4. Smokes more than 4 cigarettes or other tobacco products on a weekly basis or any type of vaping/e-cigarette use more than 4 times per week.
5. History of facial reconstructive procedures or nasopharyngeal malformation.
6. Positive for Hepatitis B or Hepatitis C infections.
7. Complete blood count (CBC) with differential outside of the NIH Department of Laboratory Medicine (DLM) normal reference range and deemed clinically significant by the PI.
8. Grade 2 or higher Hemoglobin for female participants or Grade 1 or higher Hemoglobin for male participants.
9. Chemistries in the acute care, mineral, and/or hepatic panels, and/or any of the following: lactate dehydrogenase (LDH), uric acid, creatine kinase, and total protein outside of the NIH DLM normal reference range and deemed clinically significant by the PI.
10. Urinalysis outside of the NIH DLM normal reference range and deemed clinically significant by the PI.
11. Clinically significant abnormality as deemed by the PI on ECG.
12. Clinically significant abnormality as deemed by the PI on ECHO.
13. Clinically significant abnormality as deemed by the PI on the PFT and/or spirometry.
14. Recent acute illness within 1 week of admission to the NIH CC.
15. Known allergy to any component of the interventional agent.
16. Known allergy to treatments for influenza (including but not limited to oseltamivir, nonsteroidals).
17. Known allergy to 2 or more classes of antibiotics (e.g., penicillins, cephalosporins, fluoroquinolones, or glycopeptides).
18. Receipt of influenza vaccine within 8 weeks prior to enrollment.
19. Receipt of blood or blood products (including immunoglobulins) within 3 months prior to enrollment.
20. Receipt of any unlicensed drug within 3 months or 5.5 half-lives (whichever is greater) prior to enrollment.
21. Receipt of any unlicensed vaccine within 6 months prior to enrollment.
22. Self-reported or known history of current alcoholism or drug abuse, or positive urine/serum test for drugs of abuse (i.e., amphetamines, cocaine, benzodiazepines, opiates, or metabolites, but not tetrahydrocannabinol or metabolites).
23. Self-reported or known history of psychiatric or psychological issues deemed by the PI to be a contraindication to protocol participation
24. Known close contact with anyone known to have influenza in the past 7 days.
25. Known close contact with anyone known to have COVID-19 in the past 14 days.
26. Diagnosed with COVID-19 in the 90 days prior to enrollment. The 90 days will be counted from the first positive test for SARS-CoV-2 or if a test was not done (i.e., presumptive positive), then the 90 days will be counted from the date of symptom onset.
27. Diagnosed with COVID-19 and had complications, including, but not limited to: inpatient hospitalization, required the use of oxygen, and/or on-going sequelae.
28. Non-English speaking participants.
29. Any condition that, in the judgment of the PI, is a contraindication to protocol participation or impairs the volunteer s ability to give informed consent.