Effect of Influenza Vaccination or Infection on the Development of Protective Immunity in Children

This study is a prospective surveillance of the immune response to seasonal vaccination in
healthy children. The study will enroll a total of approximately 200 subjects. 120 children
will be vaccinated with inactivated influenza vaccine (IIV) and will be divided into 4 age
cohorts: 20 children between 6-12 months of age, 40 children greater than 12 months of age
and born after 2009, 30 children with a birth date between 2006 and 2009, and 30 children
with a birth date between 2003 and 2006. 80 children presenting with natural influenza
infection prior to receipt of influenza vaccination also will be divided into 4 age cohorts:
20 children between 3-12 months of age, 20 children greater than 12 months of age with a
birth date after 2009, 20 children with a birth date between 2006 and 2009, and 20 children
with a birth date between 2003 and 2006. Influenza vaccines will be administered using
age-appropriate guidelines in all years of the study: Fluzone 0.25 mL administered
intramuscularly to children between 6 and 35 months of age and 0.5 mL to children 36 months
of age and older. Study duration is 24 months with a subject participation duration of 2
influenza seasons. The primary objective of this study is to evaluate the relationship
between influenza A virus exposure through infection and vaccination and CD4 T cell and B
cell reactivity in a cohort of young children with well documented influenza exposures. The
secondary objective is to determine the durability and breadth of the CD4 T cell response and
evaluate for relationships between response durability and factors such as age and exposure
history.

Inclusion Criteria:

1. Age:

- Between 6 and 12 months at the time of enrollment to participate in the
vaccination arm of age cohort 1A

- Between 3 and 12 months at the time of enrollment to participate in the natural
infection arm of age cohort 1B

- > 12 months, birth date after 2009 for either the vaccination (A) or natural
infection (B) arm of age cohort 2

- Birth date between 2006 and 2009 for either the vaccination (A) or natural
infection (B) arm of age cohort 3

- Birth date between 2003 and 2006 for the vaccination (A) or natural infection (B)
arm of age cohort 4

2. Gestational age of = / > 37 weeks at birth.

3. Parent/Legally Authorized Representative (LAR) can provide informed consent, with
children = / > 8 years of age providing informed assent.

4. Available for the duration of the study.

5. History of previous primary inactivated influenza vaccine (IIV) vaccination (at least
2 previous doses for age < 9 yrs, at least 1 previous dose for age 9 and older) only
for participation in the vaccination (A) arm of age cohorts 2, 3, or 4.

6. Acute illness documented by rapid influenza test, polymerase chain reaction (PCR)
testing, or testing done by either University of Rochester Medical Center (URMC) Labs
or Rochester General Hospital (RGH) Clinical Microbiology Labs to be due to influenza
virus only for participation in the natural infection arms (B) of age cohorts 1-4.

7. Children enrolled in the cohort A (vaccination cohort) are required to have age
appropriate weight and vital signs as determined by a licensed medical provider.
Children enrolled in the cohort B (natural infection cohort) are required to have age
appropriate weight and clinically stable vital signs as determined by a licensed
medical provider.

Exclusion Criteria:

1. Immunosuppression as a result of an underlying illness or condition (including the
human immunodeficiency virus (HIV) or a primary immunodeficiency syndrome).

2. Active neoplastic disease.

3. Use of potentially immunosuppressive medications currently or within the past year
(including chemotherapeutic agents) or chronic (> 2 weeks) use of oral or inhaled
steroid therapy.

4. A diagnosis of asthma requiring chronic controller medication.

5. Participation in any clinical research study evaluating an investigational drug or
therapy that is inconsistent with current standard of care within two (2) months of
enrollment in this study.

6. Previous administration of influenza vaccine in the current influenza season only for
subjects in the vaccination arm (A) of the study (subjects presenting with acute
influenza infection with vaccine failure will be eligible to enroll in the B cohorts).

7. Receipt of immunoglobulin or another blood product within the year prior to study
enrollment.

8. An acute illness within the previous 3 days or temperature > 38 degrees Celsius on
screening except for participation in the natural infection (B) cohorts.

9. A contraindication to influenza vaccination except infants between 3 and 5 months
presenting with natural influenza infection whose only contraindication is their
current age.

10. History of anemia and/or recent (within 120) hospitalization, excluding delivery and
subjects who have been hospitalized for influenza-related reasons.