Immune and Hormone Response to Influenza Vaccine

This study is an open-label, longitudinal study of healthy young women of reproductive age,
not on hormonal contraception who receive seasonal inactivated influenza vaccine (IIV). The
women will be followed for one menstrual cycle to measure luteinizing hormone surge,
estradiol, and progesterone, and then vaccinated with the seasonal inactivated influenza
vaccine prior to ovulation during a second month. At the investigator's discretion, or if
there is active circulation of influenza virus in Baltimore, the investigators will vaccinate
during the first menstrual cycle (prior to ovulation) and then follow for a second menstrual
cycle for comparison. After vaccination, they will be followed for cytokine and chemokine
responses as well as changes in the concentrations of steroid hormones. This study will
evaluate the effect of IIV on inflammatory cytokines and hormonal responses before and after
ovulation. Each woman will have 13 visits in addition to a screening visit, and will be
followed for 2 complete menstrual cycles.

Inclusion Criteria:

- Women 18-39 years of age who are in good health.

- Good general health as a result of review of medical history and/or clinical testing
at the time of screening.

- Available for the duration of the trial.

- Willingness to participate in the study as evidenced by signing the informed consent
document.

- Willing to be abstinent or to use non-hormonal methods of contraception for the
duration of the study.

- History of normal menstrual cycles (26-35 days in length) for at least 3 months.

- Willingness to refrain from routine vaccination (except as administered during study)
for the duration of the study.

Exclusion Criteria:

- Use of contraceptive pills, patch, injection or other hormonal therapies in the
preceding 3 months (6 months for DepoProvera)

- A history of hypersensitivity, including anaphylaxis to any of the components of IIV
or to eggs.

- Previous receipt of a same season licensed influenza vaccine.

- Pregnancy as determined by a positive urine or serum human choriogonadotropin (β-hCG)
test at any point during the study or in the preceding 3 months.

- Currently is lactating or breast-feeding.

- Fewer than 3 normal menstrual cycles since conclusion of last pregnancy or last use of
hormonal birth control.

- A history of autoimmune disease, or any other chronic medical condition considered
clinically significant by the investigator.

- History of HIV, Hepatitis C or active Hepatitis B.

- Known immunodeficiency syndrome.

- History of Guillain-Barré syndrome.

- Use of chronic oral or intravenous administration (≥14 days) of immunosuppressive
doses of steroids, i.e., prednisone >10 mg per day, immunosuppressants or other
immune-modifying drugs within 30 days of starting this study. (Use of topical, nasal
or inhaled steroids is permitted)

- Receipt of a live vaccine within 4 weeks or a killed vaccine within 2 weeks prior to
study start or during study.

- Receipt of blood or blood-derived products (including immunoglobulin) within 6 months
prior to study vaccination.

- Receipt of another investigational vaccine or drug within 30 days prior to study
start, or during study.

- Ongoing, daily use of analgesics or anti-inflammatory medications, including
nonsteroidal anti-inflammatories. Occasional use, and use associated with menstrual
periods is acceptable.