Recipient Inclusion Criteria:
1. Provide written informed consent before initiation of any study procedures.
2. Are able to understand and comply with all planned study procedures, including inpatient quarantine, donor-exposure sessions, infection-control procedures, symptom reporting, specimen collection, and follow-up.
3. Healthy adults aged ≥18 and ≤49 years at the time of first donor exposure.
4. Participants who can become pregnant must be practicing abstinence or using an acceptable method of contraception for at least 30 days before first donor exposure and through Day 91. A participant is considered not of childbearing potential if post-menopausal or surgically sterilized.
5. Participants who can become pregnant must have a negative serum or urine pregnancy test at screening and a negative urine pregnancy test within 24 hours before first donor exposure.
6. Are in good general health, as determined by the PI or designee, and do not have medical conditions that increase risk for influenza complications, including but not limited to:
* Chronic pulmonary disease, including asthma or emphysema.
* Chronic cardiovascular disease, including cardiomyopathy, congestive heart failure, prior cardiac surgery, ischemic heart disease, or known anatomic cardiac defects.
* Chronic medical conditions requiring close medical follow-up or hospitalization during the past 5 years, including diabetes mellitus, renal dysfunction, or hemoglobinopathies.
* Immunosuppression, ongoing malignancy, or history of malignancy, excluding non-melanotic skin cancer in remission without treatment for more than 5 years.
* Neurologic or neurodevelopmental conditions, including cerebral palsy, epilepsy, stroke, or seizures.
* History of post-infectious or post-vaccine neurologic sequelae.
* Autoimmune, inflammatory, vasculitic, or rheumatic disease, including but not limited to systemic lupus erythematosus, polymyalgia rheumatica, rheumatoid arthritis, or scleroderma.
7. Demonstrate knowledge and comprehension of the study by scoring ≥70% on a quiz of study procedures, risks, and policies.
8. Agree not to use cigarettes, e-cigarettes, marijuana, or other tobacco products during the quarantine period.
9. Agree not to use prescription or over-the-counter medications that could affect influenza susceptibility, symptoms, viral shedding, or safety assessments, including oseltamivir, zanamivir, peramivir, baloxavir marboxil, amantadine, rimantadine, aspirin, intranasal steroids, acetaminophen, decongestants, antihistamines, and other NSAIDs, within 14 days before first donor exposure and through the quarantine period, unless approved by the PI or designee.
10. Agree to avoid contact with persons at high risk for influenza complications after discharge, as instructed by the study team.
Recipient Exclusion Criteria:
11. Have household contact with, or daily contact with:
* Children under 5 years of age.
* Children or teenagers receiving long-term aspirin therapy.
* Persons who are pregnant or trying to become pregnant.
* Persons older than 65 years of age.
* Persons of any age with significant chronic medical conditions, including chronic pulmonary disease, chronic cardiovascular disease, chronic metabolic disease, renal dysfunction, hemoglobinopathy, immunosuppression, cancer, or neurologic/neurodevelopmental conditions.
12. Are healthcare workers with patient contact during the two weeks after final donor exposure or discharge from quarantine.
13. Plan to live in a confined environment, such as a ship, camp, dormitory, shelter, or other congregate setting, during the two weeks after final donor exposure or discharge from quarantine.
14. Are breastfeeding or plan to breastfeed through Day 91.
15. Have a body mass index less than or equal to 18.5 or greater than or equal to 35.
16. Smoke more than four cigarettes, e-cigarettes, marijuana, or other tobacco products on a weekly basis within 60 days before first donor exposure.
17. Have moderate or severe illness within 7 days before admission or first donor exposure, including but not limited to oral temperature ≥100°F, diarrhea, or vomiting.
18. Had laboratory-confirmed influenza in the current season or influenza-like illness in the current season.
19. Have a pulse rate less than 55 beats per minute or greater than 100 beats per minute. If the pulse rate is \<55 beats per minute and the PI or designee determines this is not clinically significant, such as in an athletic participant, and the heart rate increases to \>55 beats per minute with moderate exercise, the participant will not be excluded.
20. Have systolic blood pressure less than 90 mmHg or greater than 140 mmHg on two separate measurements.
21. Have diastolic blood pressure less than 50 mmHg or greater than 90 mmHg on two separate measurements.
22. Have long-term use, defined as ≥2 weeks, of high-dose oral glucocorticoids, defined as ≥20 mg per day prednisone or equivalent, parenteral glucocorticoids, or high-dose inhaled steroids for greater than 7 days in the last 3 months.
23. Have active HIV, hepatitis B, or hepatitis C infection.
24. Have screening laboratory test results, including white blood cell count (WBC), absolute neutrophil count (ANC), hemoglobin, or platelet count, outside the laboratory-reported normal values and deemed clinically significant by the PI or designee.
25. Have serum creatinine greater than 1.1 times the upper limit of normal.
26. Have alanine transaminase (ALT) greater than 1.1 times the upper limit of normal.
27. Have abnormal findings on screening ECG deemed clinically significant by the PI or designee.
28. Have abnormal findings on chest X-ray, if performed, deemed clinically significant by the PI or designee.
29. Have ongoing drug or alcohol abuse or dependence, or history of drug or alcohol abuse or dependence within 5 years before first donor exposure.
30. Have a positive urine or serum drug screen for cocaine, benzodiazepines, opiates, or metabolites. Positive results for tetrahydrocannabinol (THC) will not be considered exclusionary.
31. Have any medical, psychiatric, occupational, behavioral, or social condition that, in the judgment of the PI or designee, could make it difficult for the participant to comply with the protocol or could increase risk to the participant or others.
32. Have received an experimental product within 30 days before first donor exposure or plan to receive an experimental product at any time during the study.
33. Plan to enroll in another clinical trial that could interfere with study safety assessment or study endpoints during the study period, including studies involving drugs, biologics, devices, vaccines, or other interventions.
34. Plan to donate blood during the course of the study.
35. Have received the current-season influenza vaccine.
36. Have received a live vaccine within 30 days before first donor exposure or plan to receive a live vaccine before Day 31 after exposure.
37. Have received an inactivated vaccine within 14 days before first donor exposure or plan to receive an inactivated vaccine before Day 14 after exposure.
38. Have received parenteral immunoglobulin or blood products within 3 months before first donor exposure or plan to receive parenteral immunoglobulin or blood products during the study.
39. Have known close contact with anyone known to have influenza in the 7 days before screening, admission, or first donor exposure.
40. Have a known history of allergy to anti-influenza drugs required for clinical management under this protocol or allergy to more than two classes of antibiotics.
41. Have any condition that, in the judgment of the PI or designee, is a contraindication to protocol participation, interferes with compliance with study procedures, or impairs the participant's ability to give informed consent.
42. Have influenza A, influenza B, or any non-influenza respiratory pathogen detected by protocol-specified respiratory pathogen testing before donor exposure.
Donor Inclusion Criteria:
1. Provide written informed consent before initiation of any study procedures.
2. Are aged ≥18 years.
3. Tested positive by protocol-specified PCR or rapid antigen test for influenza A or B.
4. Had acute influenza-like illness or respiratory symptoms consistent with influenza within past 72 hours.
5. Symptom onset no longer than 72 hours before donor enrollment.
6. Are willing and able to comply with donor visit procedures, infection-control procedures, specimen collection, MIST or other bioaerosol sampling if performed, and donor-recipient exposure-session procedures.
7. Participants who can become pregnant must have a negative same-day urine pregnancy test before participation in recipient exposure sessions.
Donor Exclusion Criteria:
8. Have a non-influenza respiratory pathogen detected by multiplex upper respiratory pathogen testing before recipient exposure.
9. Have known active tuberculosis, current evaluation or treatment for tuberculosis, recent close contact with a person with infectious tuberculosis, cough lasting 3 weeks or longer, coughing blood or sputum from deep in the lungs, unexplained weight loss, night sweats, or other concern for active tuberculosis in the judgment of the PI or designee.
10. Have recent epidemiologic risk factors concerning for novel influenza, including close contact within the prior 10 days with sick or dead birds, poultry, livestock, dairy cattle, raw milk or unpasteurized dairy products, known animal influenza outbreaks, or known or suspected human novel influenza infection.
11. Are pregnant or breastfeeding.
12. Are clinically unstable or have clinically significant abnormal vital signs, worsening respiratory symptoms, oxygen saturation concerns, inability to tolerate study procedures, need for urgent medical evaluation, or any other medical concern that, in the judgment of the PI or designee, makes donor participation unsafe.
13. Have any medical, psychiatric, behavioral, occupational, social, or other condition that, in the judgment of the PI or designee, may interfere with completion of study procedures, make donor participation unsafe, or pose additional infectious risk to recipients.
14. Are unable or unwilling to comply with infection-control procedures or facility restrictions, including restrictions on smoking, vaping, marijuana use, or tobacco use while inside the study facility or during study procedures.
