Comparison of Three Licensed Influenza Vaccines
Condition: Influenza
MeSH terms: Influenza, Human
Study type: Interventional
Phase: Phase 4

Summary: 
      This study will evaluate in detail the way that the immune system responds to three different
      kinds of flu shots that are licensed in the United States.
    

Detailed description: 
      Previous observations to date lead to the following model: Traditional egg-derived TIV have
      contaminating internal virion proteins that preferentially elicit memory CD4 T cells specific
      for these proteins. These CD4 T cells will have limited efficacy as helpers for the
      neutralizing Ab response and will suppress the CD4 T cell response to new HA epitopes in the
      vaccine. The current study will test this hypothesis by comparing CD4 cell responses to
      specific epitopes, and the subsequent B cell and antibody response, in subjects receiving a
      vaccine containing only HA protein to vaccines with more complex antigenic characteristics.
      The CD4 T cell reactivity to pools of unique, conserved, and total pH1 HA peptides as well as
      H3, influenza B HA, NP, and M1 peptides will be quantified using cytokine Elispot assays and
      flow cytometry, and then compared to the subsequent antibody and B cell response.

      Investigators will also use this study as an opportunity to evaluate the effects of prior
      vaccination. Recent studies have emphasized the potential negative effect of vaccination in
      prior years on both the immune response as well as the protective effectiveness of current
      vaccine. In order to evaluate this phenomenon in the context of multiple vaccine
      formulations, prior vaccination history of the subjects will be reviewed and subjects
      stratify vaccination based on vaccine history.

      In addition, subjects who participated in this study in a previous year are eligible to
      re-enroll, and will receive the same vaccine that they were randomized to previously. This
      will allow an evaluation of differences between vaccine formulations in the responsiveness to
      multiple vaccinations.

      Furthermore, recent studies indicate reports that the glycosylation pattern of viral
      hemagglutinins produced in cell culture can vary depending on the host cell used, and that
      this can affect CD4 T cell immunogenicity and antibody recognition. As a cell culture-based
      influenza vaccine production platform offers many advantages and may eventually supplant the
      traditional egg-based approach, it is of great value to understand the CD4 T cell response
      induced by this vaccine and how this affects neutralizing Ab production.

      Recent data have also suggested that the failure of seasonal influenza infection to induce
      substantial levels of stalk specific antibody may be due to the relatively inaccessible
      nature of this epitope. As part of this study, investigators will also compare the
      specificity of the human antibody response between the vaccine groups, with the hypothesis
      that the rHA vaccine will more readily allow targeting of these important, broadly conserved
      epitopes. There is compelling preliminary data demonstrating that multiple antibodies that we
      have isolated have a particularly slow on rate when they bind to the HA-stalk versus the
      HA-globular head epitopes on whole virions, but not on recombinant HA trimmers expressed in
      baculovirus. The hypothesis is that a free, recombinant HA vaccine will allow more efficient
      targeting of the HA-Stalk epitopes.
    

Intervention name(s): FluBlok; Fluzone; FluCelVax; Fluzone HD
Intervention type(s): Biological; Biological; Biological; Biological
Intervention description(s): FluBlok trivalent Influenza Vaccine .5 mL given Intramuscularly; Fluzone Quadrivalent Influenza Vaccine .5 mL given intramuscularly; FluCelVax Quadrivalent Influenza Vaccine .5 mL given intramuscularly; Fluzone HD Trivalent High Dose Influenza Vaccine .5 mL given intramuscularly
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Outcomes Assessor)
Primary purpose: Basic Science