Systems Biology of Trivalent Influenza Vaccine (TIV) in Young and Elderly

RATIONALE:Trivalent Influenza vaccine (TIV) is known to induce diminished functional antibody
responses and lower protection in the elderly. Here we hypothesize that this is due to
intrinsic defects in innate responses which translates into suboptimal Hemagglutination
Inhibition Assay (HAI) titers. Therefore, early innate signatures of vaccination should
correlate with, and predict the immunogenicity of TIV in the young and elderly.

STUDY DESIGN: Single center, open label study in which adult healthy volunteers with no
contraindications to immunization will be vaccinated with TIV. Blood samples will be
collected on Days D0 (at enrollment) and D1, D3, D7, D14, D30, D180 post vaccination to study
innate and/or adaptive immunity markers. Even though influenza vaccination is considered
safe, volunteers will be asked to report any local or systemic adverse events (AEs) from Day
0 (vaccination) to Day 7 in memory aids. Reactogenicity events will also be evaluated by
injection site examination on visits at D0, D1, D3 and D7. Volunteers will be also asked to
report local and systemic AEs developing the day of a blood draw.

Additionally, only AEs considered related (unlikely, possibly, probably or definitely
related) will be collected and reported in this study from Day 0 (vaccination) to Day 180.
After Day 30 only related SAEs will be collected and reported.

Inclusion Criteria:

1. Healthy individuals aged 25-40 years, or ≥65 years old.

2. Able to understand and give informed consent.

3. Women of child-bearing potential (not surgically sterile via tubal ligation, bilateral
oophorectomy or hysterectomy or who are not postmenopausal for ≥1 year) must agree to
practice adequate contraception that may include, but is not limited to, abstinence,
monogamous relationship with vasectomized partner, barrier methods such as condoms,
diaphragms, spermicides, intrauterine devices, and licensed hormonal methods for 30
days before and 30 days after trivalent Influenza vaccination.

Exclusion Criteria:

1. Receipt of immune products:

- Receipt of blood products 3 months prior to study entry or expected receipt
through 6 months after study entry

- Receipt of any live virus vaccines within 4 weeks prior to study entry or
expected receipt within 4 weeks after study entry*

- Receipt of any inactivated vaccine within 2 weeks or expected receipt within 2
weeks after study entry*

- Receipt of the 2010-2011 influenza vaccine

2. Documented influenza infection during the 2010-2011 influenza season. Not excluded
from the study, volunteers with prior upper respiratory infections during the
2010-2011 influenza illness.

3. Presence of co-morbidities or immunosuppressive states such as:

- Chronic medical problems including (but not limited to) insulin dependent
diabetes, severe heart disease, severe lung disease, severe liver disease, severe
kidney disease, auto immune diseases, severe gastrointestinal diseases, and
uncontrolled hypertension.

- Alcohol or drug abuse and psychiatric conditions that in the opinion of the
investigator would preclude compliance with the trial or interpretation of safety
or endpoint data.

- Impaired immune function or chronic infections including (but not limited to)
HIV, hepatitis B or C; organ transplant; cancer; current and/or expected receipt
of chemotherapy, radiation therapy or any other cytotoxic or immunosuppressive
therapy [i.e. more than 10 mg of prednisone given daily or on alternative days
for 2 weeks or more in the past 3 months*; receipt of high-dose inhaled steroids
is also an exclusion criteria (nasal and topical steroids are allowed.)],
congenital immunodeficiency, anatomical or functional asplenia.

- Pregnancy or breast feeding

4. Conditions that could affect the safety of the volunteers such as:

- Severe reactions to prior vaccination with TIV, including anaphylaxis.

- History of Guillain Barré syndrome

- History of bleeding disorders

- Any allergy to any component of the vaccine including egg allergy.

5. Volunteers with any acute illness, including any fever (> 100.4 F [> 38.0C],
regardless of the route) within 3 days prior to study entry *.

6. Social, occupational, or any other condition that in the opinion of the investigator
might interfere with compliance with the study and vaccine evaluation.

- Note:

An individual who initially is excluded from study participation based on one or more of
the time-limited exclusion criteria (e.g., acute illness, receipt or expected receipt of
live or inactivated vaccines ) may be reconsidered for enrollment once the condition has
resolved as long as the subject continues to meet all other entry criteria.

Subjects receiving > 10 mg/day of prednisone or its equivalent daily or on alternate days
for more than 2 weeks may enter the study after therapy has been discontinued for more than
3 months.