Mucosal and Systemic Immunity After Viral Challenge of Healthy Volunteers Vaccinated With Inactivated Influenza Vaccine Via the Intranasal Versus Intramuscular Route

* INCLUSION CRITERIA: 1. Greater than or equal to 18 and less than or equal to 55 years of age. 2. Non-smoker. 3. Have not received influenza vaccination of any type (whether licensed or unlicensed experimental vaccine) on or after September 1, 2018. Participants who enroll in our study must be informed of the Centers for Disease Control and Prevention (CDC) recommendation to receive seasonal influenza vaccination annually. Enrollees accept that half of study participants will receive licensed approved vaccination per the usual route, and half will receive it by an unapproved route with unknown efficacy and side effects. Enrollees should not plan to receive seasonal influenza vaccination from another source from enrollment through the final study visit (Phase 2, Day 56). 4. Willingness to remain in isolation for the duration of viral shedding (at a minimum 9 days) 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 8 weeks after administration of the human challenge virus: 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 8 weeks after administration of the human challenge virus:: 1. 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. HIV uninfected with a negative test within 60 days of Phase 2, Day 0. 9. Agrees not to use IN medications (including but not limited to nasal sprays, sinus rinses), over-the-counter medications (including but not limited to aspirin, decongestants, antihistamines, and other non-steroidal anti-inflammatory drugs), and herbal medications (including but not limited to herbal tea or St. John s Wort), from 14 days prior to study enrollment through the final study visit (Phase 2, Day 56), unless approved by the investigator 10. Agrees not to donate blood or blood products from enrollment through the final study visit (Phase 2, Day 56). EXCLUSION CRITERIA: 1. Presence of 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, immune deficiency (such as IgA deficiency) or ongoing malignancy. 5. Neurological and neurodevelopmental conditions (e.g., Bell s palsy, cerebral palsy, epilepsy, stroke, seizures). 6. Postinfectious or postvaccine neurological sequelae including Guillain Barre syndrome. 7. Individual with body mass index less than or equal to 18 and greater than or equal to 40. 2. Have 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., severe asthma, chronic obstructive pulmonary disease). * Chronic cardiovascular disease (e.g., cardiomyopathy, congestive heart failure, 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., insulin-dependent diabetes mellitus, renal dysfunction, hemoglobinopathies). * Immunosuppression or cancer. * Neurological and neurodevelopmental conditions (e.g., cerebral palsy, epilepsy, stroke, seizures). * Individuals who are receiving long-term aspirin therapy. * Women who are pregnant or who are trying to become pregnant. 3. Acute illness within 7 days prior to quadrivalent IIV administration or inoculation with the human challenge virus. 4. Individuals who have grade 3 or above clinically significant laboratory values outside the limits thus specified by normal laboratory parameters. 5. Clinically significant abnormality as deemed by the PI on echocardiographic (ECHO) testing. 6. Clinically significant abnormality as deemed by the PI on the pulmonary function test (PFT). 7. Known allergy to influenza vaccination or excipients contained in the influenza vaccine used. 8. Known allergy to lidocaine or phenylephrine. 9. Known allergy to treatments for influenza (including but not limited to oseltamivir or nonsteroidal anti-inflammatory medications). 10. Known allergy to 2 or more classes of antibiotics (e.g., penicillins, cephalosporins, fluoroquinolones, or glycopeptides). 11. Anatomic or functional defects of the nasopharynx that could affect nasal sampling such as chronic rhinitis, nasal septal defect, nasal polyps or recent or remote nasal surgery 12. Receipt of blood or blood products (including immunoglobulins) within 3 months prior to enrollment. 13. Donation of blood or blood products within 3 months prior to study enrollment. 14. Receipt of any unlicensed drug within 3 months or 5.5 half-lives (whichever is greater) prior to enrollment. 15. Receipt of any unlicensed vaccine within 6 months prior to enrollment. 16. Self-reported or known history of alcoholism or drug abuse within 6 months prior to enrollment, or positive urine test for drugs of abuse (i.e., amphetamines, cocaine, benzodiazepines, opiates, metabolites, or tetrahydrocannabinol) at time of admission for viral challenge. 17. Self-reported or known history of psychiatric or psychological issues that require treatment and are deemed by the PI to be a contraindication to protocol participation. 18. Any condition or event that, in the judgment of the PI, is a contraindication to protocol participation or impairs the participant s ability to give informed consent.