H7N9 Boost in Healthy Adults

This is a Phase II, open-label study in up to 50 males and non-pregnant females, 19 to 50
years old, inclusive, who are in good health and meet all entry criteria. The study is
designed to assess the safety, reactogenicity, and immunogenicity of a single dose of a
monovalent inactivated influenza A/H7N9 virus vaccine (45 mcg of HA/0.75 mL) manufactured by
Sanofi Pasteur administered to healthy adults who previously received two doses of monovalent
inactivated influenza A/H7N7 virus vaccine manufactured by Sanofi Pasteur or one or two doses
of placebo in Protocol 07-0023. All subjects will receive a single dose of the inactivated
influenza A/H7N9 vaccine delivered intramuscularly. Reactogenicity will be measured by the
occurrence of solicited injection site and systemic reactions from the time of the study
vaccination Day 1/Visit 01 through 8 days after the study vaccination. Unsolicited
non-serious adverse events (AEs) will be collected from the time of the study vaccination
through roughly 28 days after the study vaccination. Serious adverse events (SAEs) and
new-onset chronic medical conditions will be collected from the time of the study vaccination
through roughly 6 months after the study vaccination. Immunogenicity testing against A/H7N9
and A/H7N7 antigens will include performing hemagglutination inhibition (HAI) and
neutralizing (Neut) antibody assays on serum obtained immediately prior to the study
vaccination, and roughly 8 and 28 days after the study vaccination.

An additional 60 mL of venous blood will be drawn immediately prior to the study vaccination,
and roughly 8 and 28 days after the study vaccination for exploratory cellular immunology
assays.

The duration of this study for each subject will be roughly 6 months. The primary objectives
are 1. to assess the safety and reactogenicity of a single dose monovalent inactivated
influenza A/H7N9 virus vaccine in individuals who previously received two intramuscular doses
of a monovalent inactivated influenza A/H7N7 virus vaccine or are A/H7 vaccine-naïve. 2. To
assess the serum hemagglutination inhibition (HAI) antibody responses against A/H7N9 roughly
28 days following receipt of a single dose of a monovalent inactivated influenza A/H7N9 virus
vaccine in individuals who previously received two intramuscular doses of a monovalent
inactivated influenza A/H7N7 virus vaccine or are A/H7 vaccine-naïve.

The secondary objectives are 1. To assess study-vaccine related unsolicited non-serious
adverse events following receipt of one dose of a monovalent inactivated influenza A/H7N9
virus vaccine in individuals who previously received two intramuscular doses of a monovalent
inactivated influenza A/H7N7 virus vaccine or are A/H7 vaccine-naïve. 2. To assess new-onset
chronic medical conditions following receipt of one dose of a monovalent inactivated
influenza A/H7N9 virus vaccine in individuals who previously received two intramuscular doses
of a monovalent inactivated influenza A/H7N7 virus vaccine or are A/H7 vaccine-naïve.3) To
assess the serum HAI antibody responses against A/H7N9 at baseline and about 8 days following
receipt of a single dose of a monovalent inactivated influenza A/H7N9 virus vaccine in
individuals who previously received two intramuscular doses of a monovalent inactivated
influenza A/H7N7 virus vaccine or are A/H7 vaccine-naïve. 4. To assess the serum neutralizing
(Neut) antibody responses against A/H7N9 at baseline and roughly 8 and 28 days following
receipt of a one dose of a monovalent inactivated influenza A/H7N7 virus vaccine or are A/H7
vaccine-naïve.

Inclusion Criteria:

1. Provide written informed consent prior to initiation of any study procedures.

2. Are able to understand and comply with planned study procedures and be available for
all study visits.

3. Are males or non-pregnant females, 19 to 50 years old, inclusive.

4. Are in good health*. *As determined by medical history and targeted physical
examination, if indicated based on medical history, to evaluate acute or currently
ongoing chronic medical diagnoses or conditions, defined as those that have been
present for at least 90 days, that would affect the assessment of the safety of
subjects or the immunogenicity of the study vaccination. Chronic medical diagnoses or
conditions should be stable for the last 60 days. This includes no change in chronic
prescription medication, dose, or frequency of as a result of deterioration of the
chronic medical diagnosis or condition in the 60 days prior to enrollment. Any
prescription change that is due to change of health care provider, insurance company,
etc., or that is done for financial reasons, as long as in the same class of
medication, will not be considered a deviation of this inclusion criterion. Any change
in prescription medication due to improvement of a disease outcome, as determined by
the site principal investigator or appropriate sub-investigator, will not be
considered a deviation of this inclusion criterion. Subjects may be on chronic or as
needed (prn) medications if, in the opinion of the site principal investigator or
appropriate sub-investigator, they pose no additional risk to subject safety or
assessment of reactogenicity and immunogenicity and do not indicate a worsening of
medical diagnosis or condition. Similarly, medication changes subsequent to enrollment
and the study vaccination are acceptable provided there was no deterioration in the
subject's chronic medical condition that necessitated a medication change, and there
is no additional risk to the subject or interference with the evaluation of responses
to the study vaccination. Note: Topical, nasal, and inhaled medications (with the
exception of inhaled corticosteroids as outlined in the Subject Exclusion Criteria
(see Section 5.1.2), herbals, vitamins, and supplements are permitted.

5. Oral temperature is less than 100.0F.

6. Pulse is 50 to 115 bpm, inclusive.

7. Systolic blood pressure is 85 to 150 mmHg, inclusive.

8. Diastolic blood pressure is 55 to 95 mmHg, inclusive.

9. Women of childbearing potential** in sexual relationships with men must use an
acceptable method of preventing conception*** from 30 days prior to 60 days after the
study vaccination.

**Not sterilized via tubal ligation, bilateral oophorectomy, hysterectomy or
successful Essure® placement (permanent, non-surgical, non-hormonal sterilization)
with documented radiological confirmation test at least 90 days after the procedure,
and still menstruating or <1 year of the last menses if menopausal.

***Includes, but is not limited to, sexual abstinence, monogamous relationship with
vasectomized partner who has been vasectomized for 180 days or more prior to the
subject receiving the study vaccination, barrier methods such as condoms or diaphragms
with spermicide or foam, effective intrauterine devices, NuvaRing®, and licensed
hormonal methods such as implants, injectables or oral contraceptives ("the pill).

10. Women of childbearing potential must have a negative urine or serum pregnancy test
within 24 hours prior to the study vaccination.

11. Received either two doses of an inactivated influenza A/H7N7 vaccine or one or two
doses of placebo in DMID Protocol 07-0023 or have not received an influenza A/H7
vaccine.

Exclusion Criteria:

1. Have an acute illness*, as determined by the site principal investigator or
appropriate sub-investigator, within 72 hours prior to the study vaccination.

* An acute illness which is nearly resolved with only minor residual symptoms
remaining is allowable if, in the opinion of the site principal investigator or
appropriate sub-investigator, the residual symptoms will not interfere with the
ability to assess safety parameters as required by the protocol.

2. Have any medical disease or condition that, in the opinion of the site principal
investigator or appropriate sub-investigator, is a contraindication to study
participation**.

**Including acute or chronic medical disease or condition, defined as persisting for
at least 90 days, 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 or the subject's successful completion of this study.

3. Have immunosuppression as a result of an underlying illness or treatment, or use of
anticancer chemotherapy or radiation therapy (cytotoxic) within 3 years prior to the
study vaccination.

4. Have known active neoplastic disease or a history of any hematologic malignancy.
Nonmelanoma skin cancers are permitted.

5. Have known human immunodeficiency virus (HIV), hepatitis B, or hepatitis C infection.

6. Have known hypersensitivity or allergy to eggs, egg or chicken protein, or other
components of the study vaccine.

7. Have a history of severe reactions following previous immunization with licensed or
unlicensed influenza virus vaccines.

8. Have a history of Guillain-Barré syndrome.

9. Have a history of alcohol or drug abuse within 5 years prior to the study vaccination.

10. Have any diagnosis, current or past, of schizophrenia, bipolar disease, or other
psychiatric diagnosis that may interfere with subject compliance or safety
evaluations.

11. Have been hospitalized for psychiatric illness, history of suicide attempt, or
confinement for danger to self or others within 10 years prior to the study
vaccination.

12. Have taken oral or parenteral (including intraarticular) corticosteroids of any dose
within 30 days prior to the study vaccination.

13. Have taken high-dose*** inhaled corticosteroids within 30 days prior to the study
vaccination****.

***High-dose defined as >840 mcg/day of beclomethasone dipropionate CFC or equivalent.

****Topical and nasal steroids are permissible.

14. Receipt or planned receipt of any licensed live vaccine, including seasonal influenza
vaccine, within 30 days prior to 28 days after the study vaccination.

15. Receipt or planned receipt of any licensed inactivated vaccine, including seasonal
influenza vaccine, within 14 days prior to 28 days after the study vaccination.

16. Received immunoglobulin or other blood products (with exception of Rho D
immunoglobulin) within 90 days prior to the study vaccination.

17. Received an experimental agent***** within 30 days prior to the study vaccination, or
expect to receive an experimental agent****** during the 6-month study-reporting
period.

*****Including vaccine, drug, biologic, device, blood product, or medication.

******Other than from participation in this study.

18. Are participating or plan to participate in another clinical study with an
interventional agent during the 6-month study-reporting period.

Note: Including licensed or unlicensed vaccine, drug, biologic, device, blood product,
or medication.

19. Female subjects who are breastfeeding or plan to breastfeed at any given time from the
study vaccination until 30 days after the study vaccination.

20. Blood donation or planned blood donation within 30 days prior to the study vaccination
through 30 days after the last blood drawn for this study.