Safety and Immunogenicity of a Live-attenuated Universal Flu Vaccine Followed by an Inactivated Universal Flu Vaccine

This is a prospective, multi-center, randomized, controlled, observer-blind, Phase 1 trial in
healthy male and female adults 18 through 39 years of age to evaluate safety and the immune
response of a prime boost regimen with LAIV prime and IIV boost with or without adjuvant . Up
to 65 eligible subjects will participate and will be randomized 4:3:1:3:2 to one of five
groups to receive a first dose of study cH8/1N1 LAIV (or placebo) or study cH8/1N1 IIV +
AS03A adjuvant (or placebo) followed three months later by study cH5/1N1 IIV +/- AS03A
adjuvant (or placebo).

Inclusion Criteria:

- Able to understand planned study procedures and demonstrate comprehension of the
protocol procedures and knowledge of study by passing a written examination prior to
vaccination.

- In the opinion of the investigator, can and will comply with the requirements of the
protocol (e.g., completion of the diary cards, return for follow-up visits).

- Written informed consent obtained from the subject prior to performance of any study
specific procedure.

- Male or non-pregnant female between, and including, 18 and 39 years of age at the time
of the first vaccination.

- Healthy subjects without acute or chronic, clinically significant pulmonary,
cardiovascular, hepatic or renal functional abnormality*.

- Female subjects of non-childbearing potential may be enrolled in the study.

- Female subjects of childbearing potential must have a negative pregnancy test within
24 hours of vaccination.

- Female subjects of childbearing potential must have practiced adequate contraception
for 30 days prior to first vaccination and agree to continue adequate contraception
until 2 months after completion of the vaccination series (Month 5).

- Male subjects must be surgically sterile (e.g., vasectomy) or agree to practice
adequate contraception from the first vaccination until 2 months after completion of
the vaccination series (Month 5). Please refer to the glossary of terms for the
definition of adequate contraception.

Exclusion Criteria:

- Use of any investigational or non-registered product (drug or vaccine) other than the
study vaccines.

- Any medical condition that in the judgment of the investigator would make
intramuscular injection unsafe.

- Medically diagnosed deviated nasal septum or nasal obstruction.

- Chronic administration (defined as more than 14 days in total) of immunosuppressants
or other immune-modifying drugs within 6 months before the first dose.

- Administration of long-acting immune-modifying drugs (e.g., infliximab, rituximab)
within 6 months before the first dose (Visit 03), or planned administration any time
during the study period.

- Planned administration/administration of a vaccine not foreseen by the study protocol
in the period starting 30 days before the first dose (Visit 03) up to Month 15 (Visit
15)

- Persons who should be annually vaccinated against influenza who live with or care for
persons at high risk for influenza-related complications.

- History of influenza vaccination within 6 months prior to study enrollment or
unwillingness to forego seasonal influenza vaccination during the entire study period.

- History of vaccination with an investigational pandemic influenza vaccine other than
an H1N1pdm09 vaccine.

- Any confirmed or suspected immunosuppressive or immunodeficient condition, based on
medical history and physical examination.

- Infection with human immunodeficiency virus regardless of clinical stage of
immunodeficiency.

- History of current infection with hepatitis B virus or hepatitis C virus regardless of
clinical presentation.

- History of or current autoimmune disease.

- Subjects diagnosed with excessive daytime sleepiness or narcolepsy; or history of
narcolepsy in a subject's parent or sibling.

- History of Guillain-Barré syndrome.

- History of any reaction or hypersensitivity likely to be exacerbated by any component
of the vaccines (including egg proteins); a history of anaphylactic-type reaction to
consumption of eggs; or a history of severe adverse reaction to a previous influenza
vaccine.

- Hypersensitivity to latex.

- Administration of immunoglobulins and/or any blood products during the period starting
3 months before the first dose of study vaccines or planned administration during the
study period.

- Pregnant or lactating female.

- Female planning to become pregnant or male planning to father a child or either
planning to discontinue contraceptive precautions.

- Current smoker.

- During screening, have a positive test for opiates without a prescription.

- History of chronic alcohol consumption and/or drug abuse as deemed by the investigator
to render the potential subject unable/unlikely to provide accurate safety reports.

- Have a history of convulsions or encephalomyelitis within 90 days prior to study
vaccination.

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

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

- 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.

- Have signs or symptoms that could confound or confuse assessment of study vaccine
reactogenicity.

- Any hematological or biochemical parameter that is out of range of normal, and is
considered clinically significant by the investigator.