Systems Biology of Influenza A (H5N1) Virus Monovalent Vaccine With and Without Adjuvant System 03 (AS03)

The influenza virus (a germ) causes influenza or "flu." The flu is an infection of the
breathing tubes and the lungs. In recent years, flu viruses that at first only infected birds
have begun to infect humans. One of these strains is called avian influenza (A/H5N1 subtype)
or "bird flu". Although no human cases of bird flu have been diagnosed in the United States,
this strain has caused severe illness and death in several hundred people since late 2003. .

Vaccination is the most effective way of controlling flu and preventing its illness and
complications. Vaccines help prevent illness by causing the body to make antibodies that
fight infection. One way to improve the effectiveness of a vaccine is to include a substance
that can stimulate the immune system to make more antibodies. This type of substance is
called an adjuvant; one type of adjuvant is called AS03 (Adjuvant System 03).

Inclusion Criteria:

- Individuals in good health (as determined by vital signs, medical history, physical
examination and laboratory tests);

- Able to understand and give informed consent;

- Women of childbearing potential must agree to practice adequate contraception 1 month
prior to study entry and until day 100 of the study.

Exclusion Criteria:

- Personal or family history of sleeping disorders including any of the following:
Narcolepsy with or without cataplexy; Idiopathic Hypersomnia or excessive daytime
sleepiness of unknown origin; Sleep paralysis; Sleep related hallucinations
(hypnagogic or hypnopompic hallucinations);

- Human leukocyte antigen (HLA)-DQB1*06:02 positivity (or DQB1*06 positivity if high
resolution HLA testing cannot be performed);

- An abnormal erythrocyte sedimentation rate at baseline;

- Receipt of blood products 3 months prior to study entry and until day 100 of the
study;

- Volunteers who donated blood 56 days before screening and have plans to donate on or
before day 100 of the study;

- Hemoglobin value of less than 12 mg/dL for females and less than 13 mg/dL for males;

- A positive result in the Narcolepsy Mini Screen questionnaire;

- A score of ≥11 on the Epworth sleepiness scale questionnaire;

- Receipt of any experimental agents within 6 weeks prior to first vaccination and until
the completion of the study;

- Receipt of any licensed live vaccine within 4 weeks or any licensed inactivated
vaccine within 2 weeks prior to the first study vaccination or planned receipt of any
vaccine within 42 days after study entry;

- Receipt of a H5 vaccine or AS03-adjuvanted vaccine at any time in the past prior to
current study or have a history of A/H5N1 infection;

- Influenza-like illness (ILI) or documented influenza infection during the 2013-2014
influenza season. [Not excluded from the study, volunteers with prior upper
respiratory infections other than ILI];

- Chronic medical problems including (but not limited to) insulin dependent diabetes,
severe heart disease, severe lung disease, severe liver disease, severe kidney
disease, autoimmune disease, severe gastrointestinal disease;

- 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; active cancer or any history of hematologic
cancer; receipt of chemotherapy, radiation therapy (past 36 months) or any other
potentially immunosuppressive therapy [i.e. Systemic steroids at any dose and
intra-articular administration of steroids in the past 3 months; (Nasal and topical
steroids are allowed)], congenital immunodeficiency, anatomical or functional
asplenia;

- Heart rate less than 40 bpm or greater than 100 bpm. Systolic blood pressure is less
than 90 mm Hg or equal or greater than 160 mm Hg. Diastolic blood pressure is less
than 60 mm Hg or equal or greater than 100 mg Hg;

- Pregnancy or postpartum (less than 1 year after delivery) or breast feeding;

- Severe reactions to prior vaccination with influenza virus vaccines, including
anaphylaxis;

- History of Guillain-Barré syndrome;

- A previous sudden life-threatening allergic reaction to any ingredient of Influenza A
(H5N1) Virus Monovalent Vaccine with or without AS03 adjuvant or to any of the
substances that may be present in trace amounts such as thiomersal, egg residues
including ovalbumin as well as residual amounts of sodium deoxycholate detergent,
formaldehyde and sucrose;

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

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