Eligibility Details:
- 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.