A/Texas Flu Challenge

Inclusion Criteria:

• Can understand and comply with all planned study procedures.

• Healthy, non-pregnant, non-breast-feeding persons aged ≥18 and ≤49 years of ageinclusive at the time of challenge.

• Persons biologically able to become pregnant must be practicing abstinence or usingan acceptable method of birth control for at least 30 days before the challengethrough the duration of the trial. Persons biologically able to make someonepregnant must agree not to get their partner pregnant for the duration of the trial.

• A person is considered of childbearing potential unless post-menopausal (absence of menses for ≥1 year) or surgically sterilized (tuballigation/salpingectomy, bilateral oophorectomy, or hysterectomy).

• Acceptable contraception methods for persons of childbearing potential includebut are not limited to: sexual abstinence from intercourse with partnersbiologically able to make them pregnant, monogamous relationship with avasectomized partner, barrier methods such as condoms or diaphragms withspermicide or foam, effective devices (IUDs, NuvaRing®) or licensed hormonalproducts such as implants, injectables or oral contraceptives.

• Persons of childbearing potential must have a negative serum or urine pregnancy testat screening and a negative urine pregnancy test within 24 hours before challenge.

• Are in good general health, as determined by the study investigator within 30 daysof challenge, and do not have any of the following conditions:

• Chronic pulmonary disease (e.g., asthma or emphysema).

• Chronic cardiovascular disease (e.g., cardiomyopathy, congestive heart failure,cardiac surgery, ischemic heart disease, known anatomic defects).

• Chronic medical conditions requiring close medical follow-up or hospitalizationduring the past 5 years (e.g., diabetes mellitus, renal dysfunction,hemoglobinopathies).

• Immunosuppression, ongoing malignancy, or history of malignancy (excludingnon-melanotic skin cancer in remission without treatment for more than 5years).

• Neurological and neurodevelopmental conditions (e.g., cerebral palsy, epilepsy,stroke, seizures).

• History of postinfectious or postvaccine neurological sequelae.

• Autoimmune, inflammatory, vasculitis, or rheumatic disease, including but notlimited to systemic lupus erythematosus, polymyalgia rheumatica, rheumatoidarthritis, or scleroderma.

• Demonstrate knowledge and comprehension of the study by scoring ≥70% on a quiz onthe study protocol and policies.

• Agrees to not use cigarettes, e-cigarettes, marijuana, or other tobacco productsduring the quarantine period.

• Agrees not to use prescription or over-the-counter medications that could impactinfluenza challenge efficacy or symptoms (including oseltamivir, zanamivir,peramivir, baloxavir marboxil, amantadine and rimantadine, aspirin, intranasalsteroids, acetaminophen, decongestants, antihistamines, and other NSAIDs), within 14days before challenge and through the quarantine period, unless approved by theinvestigator.

Exclusion Criteria:

• Have household contact with or have daily contact with:

• Children under 5 years of age.

• Children and/or teenagers who are receiving long-term aspirin therapy.

• Persons who are pregnant or who are trying to become pregnant.

• Persons older than 65 years of age.

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

• Chronic pulmonary disease (e.g., asthma, emphysema, COPD).

• Chronic cardiovascular disease (e.g., cardiomyopathy, congestive heartfailure, cardiac surgery, ischemic heart disease, known anatomic defects).

• Contacts who required medical follow-up or hospitalization during the past 5 years because of chronic metabolic disease (e.g., diabetes mellitus,renal dysfunction, hemoglobinopathies).

• Immunosuppression or cancer.

• Neurological and neurodevelopmental conditions (e.g., cerebral palsy,epilepsy, stroke, seizures).

• Healthcare workers with patient contact during the two weeks following the influenzachallenge.

• Plan to live in a confined environment (e.g., ship, camp, or dormitory) during thetwo weeks following the influenza challenge.

• Pregnant persons or are planning to become pregnant at any time during the study.

• Persons who are breastfeeding or plan to breastfeed at any time during the study.

• Have a body mass index (BMI) less than or equal to 18.5 or greater than or equal to

• Smoke more than four cigarettes, e-cigarettes, marijuana, or other tobacco productsweekly within 60 days before the challenge.

• Have moderate or severe illness within seven days before the challenge. Thisincludes but is not limited to an oral temperature of ≥100°F, diarrhea, or vomiting.

• Have a pulse rate of less than 55 beats per minute (bpm) or greater than 100 bpm (participants will not be excluded if the heart rate is 55 bpm with moderateexercise (e.g., walking up two flights of stairs))

• Have a systolic blood pressure of less than 90 mmHg or greater than 140 mmHg on twoseparate measurements (screening and pre-challenge).

• Have a diastolic blood pressure of less than 50 mmHg or greater than 90 mmHg on twoseparate measurements (screening and pre-challenge).

• Have long-term (≥2 weeks) use of high-dose oral (≥20 mg per day prednisone orequivalent) or parenteral glucocorticoids, or high-dose inhaled steroids for greaterthan 7 days in the last 3 months.

• Have an active HIV, hepatitis B, or hepatitis C infection.

• Have screening laboratory test results (white blood cells [WBC], absolute neutrophilcount [ANC], hemoglobin, platelets) that are outside the laboratory reported normalvalues and deemed clinically significant by the study investigator.

• Have a serum creatinine greater than 1.1 x upper limit of normal (ULN).

• Have an alanine aminotransferase (ALT) greater than 1.1 x ULN.

• Have abnormal findings on screening electrocardiogram deemed clinically significantby the study investigator.

• Have abnormal findings on screening chest X-ray deemed clinically significant by thestudy investigator.

• Have ongoing drug or alcohol abuse and/or dependence within five years of challenge.

• Have positive urine/serum test for drugs of abuse (i.e. cocaine, benzodiazepines,opiates, or metabolites).

Positive results for tetrahydrocannabinol (THC) will not be considered exclusionary. Metabolites and amphetamines as prescribed for a documented medical condition will also not be considered exclusionary.

• Have any medical, psychiatric, occupational, or behavioral problems that could makeit difficult for the participant to comply with the protocol as determined by theinvestigator.

• Have received experimental products within 30 days before the challenge or plan toreceive experimental products at any time during the study.

• Plan to enroll in another clinical trial that could interfere with the safetyassessment of the investigational product at any time during the study period,including study interventions such as drugs, biologics, or devices.

• Plan to donate blood during the study.

• Have received a live vaccine within 30 days before the challenge or plan to receivea live vaccine before Day 31 post-challenge.

• Have received an inactivated vaccine within 14 days before the challenge or plan toreceive an inactivated vaccine before Day 14 of the challenge.