Proteomic Profiling for Influenza Vaccination - FluMist
Condition: Influenza
MeSH terms: Influenza, Human
Study type: Interventional
Phase: Phase 4

Summary: 
      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.
    

Detailed description: 
      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.
    

Intervention name(s): FluMist
Intervention type(s): Biological
Allocation: Non-Randomized
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Prevention
Keywords: proteomic profiling, influenza, vaccine, FluMist