Safety, Reactogenicity and Immunogenicity of Flublok Quadrivalent (Recombinant Influenza Vaccine,Seasonal Formulation)

The U.S. Advisory Committee on Immunization Practices (ACIP) recommends that all people ≥6
months of age receive influenza vaccine annually. Recommendations for influenza
immunization of children vary somewhat among countries in the European Union, but
immunization of children at high risk for complications of influenza infection is
recommended by WHO and according to criteria in most countries. Currently, the immunization
practices are progressing to quadrivalent formulations of inactivated influenza vaccines
(IIV4) which are approved in the US for most of the indicated population. Additionally,
live attenuated vaccine (LAIV4) is approved in the U.S. for individuals aged 2-49 years and
Flublok®(RIV3), a purified trivalent recombinant hemagglutinin protein vaccine is approved
in the U.S. for adults 18-49 years of age. Children are at particular risk of complications
of influenza, including the B lineages, so expansion of the Flublok indication into the
pediatric age group with a quadrivalent formulation is warranted.

Inclusion Criteria:

1. Male or female age 6-17 years (Cohort A: 6-8 years of age; Cohort B: 9-17 years of
age)

2. Female subjects of child-bearing potential (as defined by the onset of menses) must
agree to avoid becoming pregnant and to use effective method of contraception or
practice abstinence for at least 28 day prior to the first study vaccine
administration, until the completion of the study. Female subjects of child-bearing
potential must have a negative pregnancy test within 24 hours prior to vaccine
administration.

3. In good general health, as determined by medical history and targeted physical
examination, if indicated

The parent(s) or legal representative(s) of each potential subject must:

1. Comprehend the study requirements and agree to comply with planned study procedures
and visits

2. Provide written consent prior to enrollment and initiation of any study procedures
Pediatric assent will be obtained in accordance with the Institutional Review
Board/Independent Ethics Committee determination.

Exclusion Criteria:

1. Known allergy to eggs, severe allergy (e.g. anaphylaxis) to other components of
either vaccine or contraindications to receipt of the comparator IIV4

2. Immunosuppression as a result of an underlying illness or treatment. Note: Subjects
on nasal or topical steroids will be allowed

3. Active neoplastic disease or a history of any malignancy.

4. History of receiving influenza vaccine within the past 6 months or plans during the
study to receive influenza vaccine outside of this study.

5. History of receiving immunoglobulin or other blood product within the 3 months prior
to enrollment in this study.

6. Receipt of any non-study licensed vaccines within 2 weeks (for inactivated vaccines)
or 4 weeks (for live vaccines) prior to enrollment in this study, or plans during the
study to receive a licensed vaccine within 4 weeks of a study dose [See above for
influenza vaccines].

7. Acute or chronic medical condition that, in the opinion of the investigator, would
render immunization unsafe or would interfere with the evaluation of immune responses

8. History of severe reactions following immunization.

9. An acute illness, including a body temperature greater than 100*F, within 3 days
prior to immunization.

10. Receipt of an experimental vaccine or medication within 1 month prior to enrollment
in this study, or expectation of receiving an experimental vaccine, medication, or
blood product during the study Stage in which the subject will participate.

11. Developmental delay, neurologic disorder, or seizure disorder requiring ongoing
medical management (note: history of seizure is not an exclusion criterion).

12. Any other condition or situation that would, in the opinion of the investigator,
place the potential subject an unacceptable risk of injury or render the subject
unable to meet the requirements of the protocol.

13. History of Guillain-Barré syndrome.

14. Known pregnancy, positive urine or serum pregnancy test within 24 hours prior to
planned study vaccination, or breast-feeding.

15. Concurrent participation in another clinical trial (in active or follow-up phase).