Evaluation of the Effects of Age, Prior Exposure, and Previous Vaccination on B Cell Response to Influenza Vaccine in Healthy Adults and Children

The study will be designed as a prospective surveillance of the immune response to seasonal
influenza vaccination in 240 healthy children and adults ages 9 and over. Study duration will
be 5 years, with a participant duration of 6 months. Subjects will receive Fluarix (GSK)
quadrivalent inactivated influenza vaccine, at a dose of not less than 15 ug of hemagglutinin
(HA), by intramuscular injection in open label fashion on day 0. Blood draws will occur at
baseline, day 7, 28 and 90. The primary hypothesis being tested in this study is that there
will be differences in the specificity and magnitude of the HA-specific B cell response
depending on the age, previous vaccine history and baseline B cell reactivity. The primary
objective of this study is to evaluate the relationship between first influenza A virus
exposure (inferred by age), vaccine history, and baseline serum antibody and Memory B cell
(MBC) specificity, and the magnitude and breadth of the subsequent B cell response to
seasonal influenza vaccine in healthy adults and children. The secondary objective is to
determine the durability of the antibody response and relationship between acute and durable
antibody.

Inclusion Criteria:

1. Aged equal to or greater than 9 years of age and weigh at least 50 pounds.

2. The subject must be in good health, as determined by: medical history; and targeted
physical examination, when necessary, based on medical history. Stable medical or
psychiatric condition is defined as: no recent increase in prescription medication,
dose, or frequency of medication in the last 3 months and health outcomes of the
specific disease are considered to be within acceptable limits in the last 6 months.

3. The subject is able to understand and comply with the planned study procedures,
including being available for all study visits.

4. The subject/parent has provided informed consent/assent prior to any study procedures.

5. Subjects who have not received seasonal flu vaccine for the current year.

Exclusion Criteria:

1. Subject report of known hypersensitivity to allergy to components of the study vaccine
or other components of the study vaccine.

2. Subject report of known latex allergy

3. Subject report of a history of severe reactions following previous immunization with
licensed or unlicensed influenza virus vaccines.

4. Subject report of a history of Guillain-Barre syndrome within 6 weeks of receipt of a
previous influenza vaccine.

5. The subject is a female of childbearing potential who is currently pregnant or
breastfeeding or intends to become pregnant during the study period between enrollment
and 90 days following receipt of vaccine. Pregnancy will be determined by subject
interview. Pregnancy testing is not done in this study since there is no increased
risk in pregnancy.

6. The subject is immunosuppressed as a result of an underlying illness or treatment with
immunosuppressive or cytotoxic drugs, or use of anticancer chemotherapy or radiation
therapy within the preceding 36 months.

7. The subject has an active neoplastic disease (excluding non-melanoma skin cancer or
prostate cancer that is stable in the absence of therapy) or a history of any
hematological malignancy. For this criterion, "active" is defined as having received
treatment within the past 5 years.

8. Have taken high-dose inhaled corticosteroids within 30 days prior to study
vaccination. High-dose defined as per age as using inhaled high dose per reference
chart
https://www.nhlbi.nih.gov/health-pro/guidelines/current/asthma-guidelines/quick-refere
nce-html#estimated-comparative-daily-doses

9. The subject received immunoglobulin or another blood product within the 3 months prior
to enrollment in this study.

10. The subject has received an inactivated vaccine within the 2 weeks or a live vaccine
within the 4 weeks prior to enrollment in this study or plans to receive another
vaccine within the next 28 days after vaccination.

11. The subject has an acute or chronic medical condition that, in the opinion of the
investigator or appropriate sub-investigator, would render vaccination unsafe or would
interfere with the evaluation of responses. These conditions include any acute or
chronic medical disease or conditions defined as persisting for 3 months (defined as
90 days) or longer, that would place the subject at an unacceptable risk of injury,
render the subject unable to meet the requirements of the protocol, or may interfere
with the evaluation of responses of the subject's successful completion of the study.

12. Subjects with an active infection or that has an acute illness or an oral temperature
greater than 99.9F (37.7C) within 3 days prior to enrollment or vaccination. Subjects
who had an acute illness that was treated symptoms resolved are eligible to enroll as
long as treatment is completed and symptoms resolved > 3 days prior to enrollment.

13. The subject is currently participating or plans to participate in a study that
involves an experimental agent (vaccine, drug, biologic, device, blood product, or
medication) or has received an experimental agent within 1 month prior to enrollment
in this study, or expects to receive another experimental agent during participation
in this study, or intends to donate blood during the study period.

14. The subject has any condition that would, in the opinion of the site investigator,
place the subject at an unacceptable risk of injury or render the subject unable to
meet the requirements of the protocol.

15. The subject has a history of alcohol or drug abuse in the 5 years prior to enrollment.

16. The subject has a known human immunodeficiency virus, hepatitis B, or hepatitis C
infection.

17. Subject weighs less than 50 lbs.

18. Subject expects to have a medical procedure during the upcoming 8 weeks that estimates
blood loss to exceed 400 cc for adults or for children would exceed 3 ml/kg.