Studying Cell Immune Responses to a Live Flu Vaccine in Healthy Adults
Condition: Normal Physiology
Study type: Observational

Summary: 
      Background:

      - One form of the influenza vaccine is a nasal spray. It uses a live but weakened flu virus.
      Researchers want to better under how the live vaccine interacts with the body s immune
      system. They will test the nasal spray flu vaccine (called FluMist) against a saline (salt
      water) nasal spray. They will then look at blood and nasal cell samples to see how the
      vaccine affects these cells immune response.

      Objectives:

      - To look at immune changes in nasal and blood cells in people who receive live flu vaccine.

      Eligibility:

      - Healthy volunteers between 18 and 49 years of age.

      Design:

        -  Participants will have five outpatient visits for this study. Each visit will last up to
           2 hours.

        -  At the first visit, participants will have a physical exam and medical history. They
           will give blood and urine samples. Nasal cell samples will also be collected.

        -  A week later, participants will have either the nasal spray flu vaccine or a saline
           spray. They will know which spray they will receive. Blood samples will be collected.

        -  Two days after the vaccination, they will have another physical exam. Blood and nasal
           cell samples will be collected.

        -  At the final two visits (1 week and 1 month after the vaccination), more blood samples
           will be collected.

        -  Those who had the saline spray will be able to have the actual vaccine spray at the last
           study visit.

        -  The ratio of participants who receive vaccine to those who receive saline will be 4:1.
    

Detailed description: 
      Two types of influenza vaccines are currently licensed in the US, trivalent inactivated
      vaccine (TIV), administered by intramuscular injection, and LAIV, administered by nasal
      spray. Both vaccines are safe and effective in their approved age groups. Neutralizing
      antibody in the serum has been found to be a correlate of protection for TIV, but the immune
      correlates of protection for LAIV are not known. Defining the origin and nature of
      transcriptional responses to LAIV in URT in infected and bystander epithelial and lymphocyte
      cells in healthy adults will be a highly informative first step in a systems approach toward
      understanding the molecular basis of viral replication restriction and the regulation of the
      local mucosal immune responses following LAIV administration.

      This natural history study will use a systems biology approach to identify LAIV replication
      niches among a variety of URT cell types and characterize the host immune response to LAIV.
      Healthy volunteers aged 18-49 years will be prescreened for low (<1:10) serum HAI titer
      against the component influenza vaccine virus strains (influenza A H1N1 and H3N2, and
      influenza B) of the licensed seasonal LAIV. Ten HAIlow or -negative individuals will be
      vaccinated intranasally with LAIV (n=8) or will receive saline intranasally (n=2). One week
      prior to and 2 days after vaccine administration, an NP specimen will be collected using
      flocked NP swabs. A blood sample will be collected at the time of NP swabbing and on Days 7
      and 28 after vaccination. Total subject participation time from enrollment/baseline to the
      final study visit will be 5 weeks.

      We propose to recover cells from NP swab samples and sort individual cells of different
      subsets based on specific surface phenotypic markers. We will then utilize
      microfluidics-based real-time reverse transcriptase polymerase chain reaction (rRT-PCR) to
      quantify transcripts from bulk and single cells. These transcripts will include
      strand-specific influenza RNA for determining virus replication, genes for assigning cells to
      specific epithelial or lymphocyte subpopulations, selected genes in the IFN signaling
      pathways to determine innate immune responses, and genes involved in activation and effector
      functions of different immune cell subsets. Results will be analyzed with several
      bioinformatics tools, with an emphasis on the differential signaling responses between
      various cells types. The mucosal transcriptional data will be correlated with B and T cell
      immunity markers and traditional serology (HAI and neutralization assays) before and after
      vaccination to identify key factors affecting the immune response to LAIV.
    

Observational model: Other
Time perspective: Prospective
Keywords: Nasal Spray Vaccine; Nasal Cells