Influenza Vaccine Challenge Study in Healthy Subjects
Influenza Vaccine Challenge Study in Healthy Subjects
The purpose of this research is to study the safety, tolerability and effectiveness of the
 investigational influenza vaccine in healthy volunteers infected with an attenuated influenza
 A virus.
The investigational influenza vaccine (FLU-v) contains multiple highly conserved T cell
 epitopes that are present on most influenza viruses, which have been identified as reactive
 in different human leukocyte antigen (HLA) populations; thus making it unlikely that anybody
 in the vaccinated population would be unable to mount an immune response to at least one of
 the epitopes contained in the vaccine.

 In this study up to 44 will be vaccinated with the FLU-v experimental vaccine or a placebo in
 a 1:1 ratio. Volunteers will attend a screening visit, a vaccination visit, a 10-11 day
 overnight stay in a quarantine facility, and a follow-up visit to the P1 clinic.

 Three weeks after being vaccinated with FLU-v or placebo, 30 volunteers will be taken to a
 Quarantine Unit to be exposed to the attenuated H3N2 study virus and then monitored by study
 physicians and nurses for a 10-11 day period. The other 14 volunteers will be held in reserve
 as back-ups. If fewer than 30 of the volunteers who travel to the Quarantine Unit are
 eligible to be exposed to the study virus, then volunteers who have been kept in reserve will
 be used.

 Following discharge from the Quarantine Unit, volunteers will attend one study follow-up
 visit, 28 days after exposure to the study virus. Assessments will take place and samples
 will be taken from volunteers.
Inclusion Criteria:

 -  General good health determined by a screening evaluation ≤120 days prior to IMP
 administration and on the day of admittance to quarantine

 -  Using methods of contraception, (e.g. spermicidal gel plus condom) for the entire
 duration of the study, up to the Study Completion visit, and refrain from fathering a
 child in the three months following study drug administration.

 -  Negative HIV, hepatitis B and C antibody screens

 -  Negative class A drugs, alcohol and nicotine screen

 -  Seronegative (≤10 HAI) for challenge virus

 -  Have not been vaccinated for influenza virus since 2006 (as determined in the medical
 history) or had a known influenza-like illness in the current season, defined as in
 the last 12 months

 Exclusion Criteria:

 -  Presence of any significant acute or chronic, uncontrolled medical or psychiatric
 illness, including but not exclusive to the conditions listed in Appendix 2, that in
 the view of the Investigator is associated with increased risk of complications of
 respiratory viral illness

 -  Abnormal pulmonary function as evidenced by clinically significant abnormalities in
 spirometry

 -  Presence of household member or close contact who is: less than 3 years of age; known
 immunodeficient; receiving immunosuppressants; undergoing/soon to undergo
 chemotherapy; diagnosed with emphysema or COPD; is elderly residing in a nursing home;
 severe lung disease or medical condition; received a transplant (bone marrow or solid
 organ)

 -  History of asthma, COPD, pulmonary hypertension, reactive airway disease, or any
 chronic lung condition of any aetiology

 -  Any laboratory test or ECG which is abnormal and deemed by the investigator to be
 clinically significant

 -  Venous access inadequate for phlebotomy demands

 -  Regular daily smokers during the 6 months prior to study entry or those who have a
 significant history of any tobacco use at any time

 -  Subject is diabetic

 -  History or evidence of autoimmune disease or known impaired immune responsiveness

 -  Recent and/or recurrent history of autonomic dysfunction

 -  Receipt of systemic glucocorticoids, antiviral drugs, immunoglobulins or blood
 transfusions within 1 month, or any other cytotoxic or immunosuppressive drug within 6
 months prior to vaccination. Receipt of any systemic chemotherapy agent at any time

 -  Presence of any febrile illness or symptoms of upper or lower tract respiratory
 infection in the 28 days prior to viral inoculation

 -  Any anatomic or neurological abnormality impairing the gag reflex or associated with
 an increased risk of aspiration, or history suggestive of such a problem or any
 abnormality significantly altering the anatomy of the nose or nasopharynx

 -  Known IgA deficiency, immotile cilia syndrome, or Kartagener's syndrome

 -  Nasal or sinus surgery within 30 days prior to vaccination

 -  Significant history of seasonal hay fever or a seasonal allergic rhinitis (SAR), or
 perennial allergic rhinitis (PAR), or chronic nasal or sinus condition

 -  Acute and/or chronic use of any medication or other product for symptoms of rhinitis
 or nasal congestion or for any chronic nasopharyngeal complaint, or chronic use of any
 intranasal medication for any indication

 -  Use of any prescription drugs, herbal supplements, within 4 weeks prior to vaccine
 administration

 -  Receipt of any investigational drug within 3 months, or prior participation in a
 clinical trial of any influenza vaccine, medication or experimental Influenza viral
 challenge delivered directly to the respiratory tract within 1 year

 -  Previous exposure to the IMP or similar substance

 -  History of multiple and recurring allergies and/or adverse reaction to any components
 of the IMP and challenge virus preparation

 -  History of allergy or intolerance to the following drugs: oseltamivir or zanamivir.

 -  Allergic to gentamicin