Proteomic Profiling for Influenza Vaccination - FluMist
Proteomic Profiling for Influenza Vaccination - FluMist
The purpose of this study is to look at changes that occur in blood and nasal swab samples
 after a person's immune system responds to receiving a flu vaccine. The investigators will
 look at the immune response in 50 healthy volunteers, between 21 and 49 years of age, after
 they have been vaccinated with 1 dose of a flu vaccine sprayed into the nose. A blood sample
 and nasal swab of each nostril will be collected from volunteers before they receive the flu
 vaccination. After receiving the flu vaccine, volunteers will record health changes and daily
 temperatures on diary cards at home for 21 days. Blood will be drawn and nasal swabs will be
 collected from each volunteer at each of the 6 study visits. Volunteers will participate in
 the study for approximately 1 month. This study is being conducted at the Glennan Center for
 Geriatrics and Gerontology at Eastern Virginia Medical School.
This is a nonrandomized, non-comparative study conducted in 50 healthy subjects, between 21
 and 49 years of age, who have been vaccinated with 1 dose (0.5 mL) of Influenza Virus Vaccine
 Live, Intranasal FluMistTM, a live trivalent nasally administered vaccine. The central
 hypothesis is that immune responses to vaccination can be quantified by proteomic profiling
 of serum and nasal proteins, and that host responses to different infectious agents are
 unique and can be "fingerprinted" by proteomics. Using influenza virus vaccination, this
 study proposes to use mass spectrometry platforms to profile and characterize proteins from
 serum samples obtained from recipients. These samples will be used to develop a proteomic
 profiling system for monitoring vaccine response, and will eventually allow earlier
 detection/diagnosis of infection. Annually, natural influenza infections cause serious
 international public health problems that are particularly severe in elderly people, who
 account for more than 90% of influenza mortality. The current trivalent split virus influenza
 vaccine is cost-effective, but its efficacy is greatly reduced in the elderly population. The
 long-term goal of the investigators' approach is to develop tools useful for reducing the
 morbidity and mortality of influenza from natural and potential bioterrorism-related
 infections by improving measures of vaccine efficacy and early diagnosis. This study is being
 conducted at the Glennan Center for Geriatrics and Gerontology at Eastern Virginia Medical
 School. Solicited adverse events (AEs) and daily temperatures will be collected on diary
 cards for 21 days. Unsolicited AEs will also be collected throughout the duration of the
 study. Blood will be drawn and nasal swabs will be collected from each subject at each of the
 6 study visits. Subjects will participate in the study for approximately 1 month. The primary
 objective of this study is to analyze serum samples before and after FluMist intranasal
 attenuated live-virus influenza vaccination to identify surrogate markers reflective of the
 immune response by using surface-enhanced laser desorption/ionization-time of flight
 (SELDI-TOF) and matrix-assisted laser desorption/ionization-time of flight (MALDI-TOF) mass
 spectrometry proteomic profiling tools reflective of the immune response. Concurrent T-cell
 activation, cytokine assays, and hemagglutination inhibition (HI) serologic assays will
 correlate cellular and humoral responses to influenza vaccination with protein profiling
 changes. Proteins obtained from intranasal swabs pre and post vaccination will be analyzed.
 The investigators anticipate identifying multiple host response proteins from this analysis
 using combinations of gel electrophoresis, MALDI-TOF and tandem MS/MS approaches. The
 secondary objective is safety. Data on solicited reactions will be collected from Day 0 to
 Day 14. The time of occurrence of AEs will be used to determine if there is a correlation
 with the time of increase in certain protein biomarkers. The primary endpoint is to identify
 surrogate markers reflective of the immune response in serum and/or nasal proteins and to
 correlate these markers to cellular and humoral responses (demonstrated with T-cell
 activation, cytokine assays, and the hemagglutination inhibition [HI] serologic assays) to
 influenza vaccination. The secondary endpoint is safety. Data on local reactions and
 solicited systemic reactions will be collected from Day 0 to Day 14 and categorized according
 to severity. Unsolicited AEs will be collected and categorized throughout the study by
 severity, duration, and relatedness to vaccine. The time of occurrence of AEs will be used to
 determine if there is a correlation with the time of increase in certain protein biomarkers.
Inclusion Criteria:

 1. Subject is between the ages of 21 to 49 years of age on day of enrollment, visit 1(day
 0).

 2. Provides written informed consent.

 3. Subject is judged to be healthy on the basis of verbal medical and concomitant
 medications history and has been medically stable prior to screening

 4. Subject is able to attend scheduled visits and to comply with the study procedures
 during the entire duration of the study and will be available for 1 month after
 enrollment.

 5. Female is not at risk of pregnancy, based on the following:

 1. Utilizing adequate method of birth control and agree to continue using this
 method for at least 1 month after enrollment. Adequate methods of birth control
 may include hormonal (oral, transdermal, or injectable) or double barrier methods
 (eg condom with spermicide, vaginal combined ring) or intra-uterine device. If
 using hormonal method or intra-uterine device, usage should be stable for 1 month
 prior to vaccination and should continue for 1 month post vaccination.

 2. Negative urine pregnancy test is required for all females at study entry. Females
 surgically sterilized (history of tubal ligation or total or subtotal
 hysterectomy) or post-menopausal for 2 years must still have a negative pregnancy
 test at time of enrollment.

 6. Subject should be available through telephone contact and agree to participate in all
 scheduled visits.

 Exclusion Criteria:

 1. Adults younger than 21 years of age or 50 years and older

 2. Subject had physician-diagnosed (preferably by culture) influenza at any time during
 the past 2 years.

 3. Subject received an influenza vaccine in the 6 months preceding enrollment in the
 study

 4. Subjects who receive any live virus vaccine within one month of enrollment and any
 inactivated or subunit vaccine within 2 weeks of enrollment or with plans to receive
 any vaccine during this study will be excluded from the study, eg, pneumococcal
 vaccine.

 5. Subject received blood or blood products in the last 3 months.

 6. Subject has asthma or reactive airway disease.

 7. Subject has a history of any serious vaccine reactions or anaphylaxis or reactions
 likely to be exacerbated by any component of the study vaccine,

 8. Subject is allergic to eggs, egg products or gentamycin.

 9. Subject has known or suspected disease(s) of the immune system with immunosuppression,
 eg, rheumatoid arthritis, systemic lupus erythematosus (SLE), lymphoma, human
 immunodeficiency virus (HIV), cancer diagnoses or treatment within the last 5 years
 (except skin cancer), etc.

 10. Subject is currently being treated with an immunosuppressive medications (ie, cancer
 therapeutic agents such as tamoxifen, systemic corticosteroids such as prednisone, and
 arthritis medications such as methotrexate). Please note that inhaled or topical
 corticosteriods are acceptable.

 11. FluMist recipients in close contact (eg, within the same household) with
 immunocompromised individuals during periods in which the immunosuppressed person
 requires care in a protective environment. (contact should be avoided for at least 21
 days). Contact with small children is not an exclusion. Females who breastfeed are
 excluded.

 12. Drug interactions: On antiviral therapy in 48 hours preceding scheduled vaccination

 13. Antiviral agents administered until 3 weeks after FluMist vaccination.

 14. Participation in any other interventional drug or vaccine trial within 30 days prior
 to enrollment. Therefore subject is not to receive other investigational products
 (drug or vaccine) during the length of their participation in the trial.

 15. Subject has acute respiratory illness. Administration of FluMist should be postponed
 until after the acute phase (at least 72 hours) of respiratory illnesses.

 16. Subject has active infections or illnesses.

 17. Subject had an acute illness with or without fever (temperature >/= 99.5 F [oral]) in
 the 72 hours preceding vaccination. Administration of FluMist should be postponed
 until after the acute phase (at least 72 hours) of febrile and/or acute illnesses.

 18. Subject has acute or chronic medical health condition that, in the opinion of the
 investigator, would render vaccination unsafe or would interfere with the evaluation
 of responses. These conditions include, but are not limited to health problems
 associated with

 1. heart disease, (if heart failure is present, New York Heart Association
 Functional Class III or IV),

 2. kidney disease, (history of significant renal impairment e.g., dialysis and
 treatment for kidney disease, including diabetic and hypertensive kidney
 disease),

 3. chronic liver disorders (e.g. hepatitis B or C),

 4. diabetes mellitus (excluding diet-controlled diabetes),

 5. arteriosclerotic event during the 6 months prior to enrollment (eg, history of
 myocardial infarction, stroke, recanalization of femoral arteries, or transient
 ischemic attack),

 6. functional or anatomic asplenia,

 7. cancer diagnosed and treated within the past 5 years with chemotherapy, radiation
 therapy and/or surgery

 8. significant anemia or other blood disorders.

 9. Underlying unstable chronic disease e.g.uncontrolled hypertension (systolic blood
 pressure >180 mm Hg or diastolic blood pressure >100 mm Hg at Visit 1), etc.

 19. Subject has any active neurologic disorders (ie, encephalopathy, optic
 neuritis/neuropathy, partial facial paralysis, and brachial plexus neuropathy).

 20. Subject is pregnant or planning to become pregnant within the next 2 months.

 21. Subject is breastfeeding.

 22. Subject has any condition that would, in the opinion of the site investigator, place
 the subject at an unacceptable risk of injury or render the subject unable to meet the
 requirements of the protocol.

 23. Subject has a prior history of Guillain-Barré syndrome.

 24. Subject has a history of drug or alcohol abuse.