T-cell Response-Flu Risk in Older Adults
Condition: Influenza
MeSH terms: Influenza, Human
Study type: Interventional

Summary: 
      The purpose of this study is to determine how the immune system changes with aging and makes
      influenza a more serious illness in older people. Influenza vaccination not only can protect
      people from getting the flu but also can lessen the severity of the illness. This is
      particularly true for people with congestive heart failure (CHF). This research may provide
      information that could eventually lead to a new laboratory test that will predict how
      effective vaccination is for preventing influenza illness in older people. Volunteer
      participants in this study will include the following groups: 1) healthy young adults 20 - 40
      years old; 2) older adults, 60 years and older, without a history of CHF; 3) older adults, 60
      years and older, with a history of CHF. All study participants will be vaccinated with the
      current preparation of inactivated influenza vaccine. A small amount of blood will be drawn
      before each vaccine and at 4, 10, and 16-20 weeks afterward.
    

Detailed description: 
      This study will increase the understanding of how age, congestive heart failure (CHF) or a
      prior hospitalization for an influenza-related acute coronary event affect the immune
      response to influenza vaccination. By elucidating the defects in the immune response to
      influenza vaccination that are associated with the subsequent influenza illness, these
      methods can be used to screen subsets of older adults to establish the risk profile related
      to influenza in that population, to target these defects for future vaccine development and
      to use these methods as surrogates of protection to screen potential vaccines prior to
      conducting large scale clinical trials to establish clinical efficacy. The primary objective
      is to show that granzyme B (Grz B) levels in influenza virus-stimulated peripheral blood
      mononuclear cell cultures are lower in older adults who receive inactivated influenza vaccine
      (IIV) and subsequently develop influenza illness compared to those who do not. Secondary
      objectives are to: (1) establish a cut-off value for Grz B as a marker of increased risk for
      influenza illness; (2) show that interferon-gamma (IFN-gamma) levels are lower and
      interleukin-10 (IL-10) levels are higher in influenza virus-stimulated peripheral blood
      mononuclear cell cultures from vaccinated older adults who subsequently develop influenza
      illness compared to those who do not; (3) determine the effect of macrophage migration
      inhibitory facator (MIF) on T-cell responses to influenza vaccination; (4) determine the
      association between CHF and ischemic heart disease (IHD) including acute coronary syndromes
      and the immune response to influenza vaccination; (5) determine the effect of functional
      status measured by the Six-Minute Walk Test (SMWT) on immune responsiveness to influenza
      vaccination; (6) determine the effect of medications with anti-inflammatory effects including
      angiotensin converting enzyme inhibitors (ACEI) and cholesterol-lowering drugs (statins) on
      immune responsiveness to influenza vaccination; (7) evaluate the effect of the age-related
      decline in the expression of the costimulatory molecule, CD28, on cytotoxic T-lymphocytes, on
      the Grz B response to influenza vaccination; (8) study the potential role of
      activation-induced cell death (AICD) on the T helper type 1 (Th1: IFN-gamma) versus T helper
      type 2 (Th2: IL-10) response to influenza vaccination; (9) determine in vitro whether or not
      co-stimulatory molecules such as 4-1BB ligand or CD70 can be used to augment the cytokine,
      Grz B or CTL responses to influenza vaccines in older adults; (10) determine in vitro whether
      or not heat shock proteins (HSP) can be used to augment the cytokine and/or Grz B response to
      influenza vaccination in older adults; (11) determine in vitro whether or not heat shock
      proteins (HSP) can be used to augment the cytokine and/or Grz B response to influenza
      vaccination in older adults who develop influenza illness in spite of influenza vaccination;
      and (12) determine in vitro whether or not heat shock proteins (HSP) increase the frequency,
      Grz B content or proportion of influenza virus-specific CTL expressing CD28 in vaccinated in
      older adults. The study group will consist of 150 adults, age 60 years and older,
      characterized according to age, presence of CHF or IHD, or (to be identified in the prior
      influenza season) an admission with an acute coronary syndrome or exacerbation of CHF. All
      subjects will be vaccinated in the fall of each year with the current preparation of
      trivalent, split-virus influenza vaccine. Serum antibody titers, serum cytokine levels, ex
      vivo levels of IFN-gamma and IL-10, and ex vivo and in vitro levels of Grz B in
      influenza-stimulated peripheral blood mononuclear cell at pre-vaccination and
      post-vaccination (4, 10 and 16-20 weeks) time points will be compared in subjects who do and
      do not get influenza illness. The peak as well as the duration of response to vaccination for
      each of the immunologic measures will be determined.
    

Intervention name(s): Commercial TriValent Split Influenza Virus
Intervention type(s): Biological
Allocation: Non-Randomized
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Prevention
Keywords: Influenza, T cell, vaccine, Congestive heart failure