The purpose of this study is to evaluate a new method of detecting the flu infection. This
method may allow researchers to identify new proteins being made in response to an infection
even before symptoms of the infection are present. The goal of this study is not to prevent
the flu but to monitor the immune system response. The elderly and those with chronic health
problems are at greater risk for complications (i.e., pneumonia, bronchitis [bacterial
infection in the lungs], and sinusitis [bacterial infection in the sinuses]) from the flu.
Early detection and diagnosis of the flu decreases the number of people with these
complications. Participants will include healthy people between the ages of 21-40, between
the ages of 60-89, or 90 years and older, who are living in the communities surrounding the
3 study sites in Virginia. There will be 5 study visits, and subjects will participate up to
The central hypothesis of this study is that immune responses to vaccination can be
quantified by proteomic profiling of serum (and other clinical fluids), and that the 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, eventually, early detection/diagnosis of infection. The long-term goal of this
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. The primary objective is to use surface-enhanced laser
desorption/ionization time-of-flight (SELDI-TOF) mass spectrometry and matrix-assisted laser
desorption/ionization time-of-flight (MALDI-TOF) mass spectrometry proteomic profiling tools
to analyze a series of serum samples obtained from cohorts of young and elderly subjects,
before and after trivalent split-virus influenza vaccination, to identify surrogate markers
reflective of the immune response. The secondary objective is to use concurrent T-cell
activation, cytokine assays, and hemagglutination inhibition (HI) serologic assays to
correlate cellular and humoral responses to influenza vaccination with protein profiling
changes. Comparisons of the protein profile data with the T-cell activation, cytokine
assays, and HI results will be evaluated using multiple classification algorithms, and
potential biomarker proteins will be identified by sequencing with either a MALDI-TOF or
electrospray ionization mass spectrometer. Study Participants will include healthy adult
volunteers between the ages of 21-40, between the ages of 60-89, or 90 years and older, who
are living independently in the communities surrounding the 3 study sites in Virginia. There
will be 5 study visits, and subjects will be in the trial for up to 1 month. The primary
endpoint of the study is to identify surrogate markers reflective of the immune response and
to correlate these markers to cellular and humoral responses (demonstrated with T-cell
activation, cytokine assays, and the HI serologic assays) to influenza vaccination. The
secondary endpoint is safety. Data on the following solicited local reactions (injection
site pain, bruising, redness, tenderness, and induration) and solicited systemic reactions
(fever, headache, malaise, myalgia, cough, runny nose, chills, vomiting, arthralgia, rash,
and diarrhea) will be collected from Day 0-Day 14 and categorized as none, mild, moderate,
and severe. Unsolicited adverse events (including serious adverse events) will be collected
and categorized throughout the study by severity, duration, and relatedness to the vaccine.
1. Males or females 21 to 40 years of age or between the ages of 60 and 89, or 90 years
or older on the day of inclusion.
2. Provides written informed consent.
3. Subject is judged to be healthy on the basis of verbal history.
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
5. Females of childbearing potential must agree to use contraception and must agree to
continue using this method for at least 3 months after enrollment. All females under
the age of 60 must have a negative urine pregnancy test at enrollment. Those that
have a history of tubal ligation or hysterectomy or are postmenopausal at least 1
year of no menses may be included but must still have a negative urine pregnancy test
at enrollment. Acceptable forms of hormonal contraception include the use of oral
contraceptives, injectable contraceptives (ie, Depo-ProveraTM) or transdermal
contraceptives for a period of 3 months prior to enrollment.
6. Subject must have access to telephone service.
1. Subject received an influenza vaccine 6 months preceding enrollment in the study.
2. Subject had physician-diagnosed (preferably by culture) influenza at any time during
the past 2 years.
3. Subject had an acute illness with or without fever (temperature greater than or equal
to 99.5ºF [oral]) in the 72 hours preceding vaccination.
4. Subject received any vaccine 14 days before enrollment or plans to receive any
vaccine during this study.
5. Subject received blood or blood products in the last 3 months.
6. Subject has known or suspected disease(s) of the immune system (ie, rheumatoid
arthritis, lupus, lymphoma, human immunodeficiency virus, etc). Stable, controlled
osteoarthritis is allowed if medication is only intermittently used for relief of
Subject has underlying unstable chronic disease such as uncontrolled hypertension
(systolic blood pressure >180 mm Hg or diastolic blood pressure >100 mm Hg at Visit
1), congestive heart failure, heart attack within the last 6 months, liver, and
kidney disease, etc;
7. Subject is currently being treated with an immunosuppressive medications (i.e.,
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.
8. Subject is pregnant or planning to become pregnant within the next 2 months.
9. Subject is breastfeeding.
10. Subject has a history of allergic disease or reactions likely to be exacerbated by
any component of the study vaccine, including a history of anaphylaxis or serious
vaccine reaction; subject is allergic to eggs, contact lens solution, or has ever had
a severe reaction to any influenza vaccine.
11. Subject is allergic to latex rubber;
12. Subject has an acute or chronic medical 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: history of
significant renal impairment (dialysis and treatment for kidney disease, including
diabetic and hypertensive kidney disease); diabetes mellitus (excluding
diet-controlled diabetes); cardiac insufficiency, if heart failure is present (New
York Heart Association Functional Class III or IV); arteriosclerotic event during the
2 weeks prior to enrollment (eg, history of myocardial infarction, stroke,
recanalization of femoral arteries, or transient ischemic attack); functional or
anatomic asplenia; cancer (excluding breast, skin, and prostate cancer diagnosed and
treated more than 5 years prior to inclusion).
13. 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.
14. Subject has acute respiratory or other active infections or illnesses.
15. Subject has any active neurologic disorders (ie, encephalopathy, optic
neuritis/neuropathy, partial facial paralysis, and brachial plexus neuropathy).
16. Subject has a prior history of Guillain-Barré syndrome.
17. Participation in any other interventional drug or vaccine trial within 30 days prior