Elderly Influenza Vaccine Immunogenicity Substudy
Condition: Influenza
MeSH terms: Influenza, Human
Study type: Observational

Summary: 
      The body's immune system (fights infection) is known to decline during the aging process,
      resulting in an increased risk of catching infections. Vaccinations also are not as effective
      in protecting older people against infection as they are in younger people. The purpose of
      this study is to better understand how and why vaccines are not as effective in older people.
      The researchers believe that the immune response in older people who get a higher dose
      vaccine will be similar to the immune response in young adults who get the standard (lower)
      dose vaccine. This study is a substudy to a main study, evaluating flu vaccines in people 65
      years and older. Volunteers who are in the main study will be asked if they will participate
      in the substudy. The substudy requires them to give 2 additional blood samples for an
      in-depth look at their immune response to the flu vaccine given in the main study. Substudy
      volunteers will have up to 3 clinic visits and participate up to 28 weeks.
    

Detailed description: 
      There is a need to increase protection against influenza conveyed to elderly persons by
      inactivated influenza virus vaccines. Serum antibody titer is the primary surrogate marker
      for immunity to influenza after vaccination; and increasing the antigen dose has been shown
      to increase the serum antibody response in vaccinated persons, including the elderly. However
      it is not known how the remainder of the immune system responds to the higher dose of
      influenza antigen. This study is linked to DMID protocols 04-100 and 05-0055. This study will
      be conducted as a substudy of DMID 04-100 at the University of Maryland, Baltimore. Subjects
      ages 65 years and older, who meet the entry criteria for the primary study, will be
      approached for participation in an immunology substudy of volunteers who receive a single
      intramuscular injection of either the high-dose or standard-dose of licensed 2004-2005
      trivalent inactivated influenza vaccine. A minimum of 30 elderly subjects (with the
      possibility of up to 60 elderly subjects) will be enrolled for the substudy. The substudy
      will require an extra 100 ml (total blood draw of 120 ml) of blood drawn from the same 20 ml
      venipuncture obtained for hemagglutination inhibition assay (HAI) titers (as per the primary
      study) on days 0 and 28. To minimize adverse side effects, the additional 100 ml of blood
      required for the substudy will be obtained from the same venipuncture site from which the 20
      ml blood will be obtained for HAI titers (i.e., if blood collection stops after the 20 ml for
      HAI are drawn, the researchers will not attempt to obtain additional blood from a separate
      venipuncture site). Subjects' blood will be evaluated for key humoral and cell-mediated
      immunity (CMI) responses to better understand the mechanisms underlying the predicted
      suboptimal immune responses to one or more of the three influenza vaccine antigens observed
      in the elderly. With regard to specific study objectives, blood samples will be submitted for
      the following analysis: (1) measurement of serum anti-HA (hemagglutinin) IgG and IgA
      antibodies by ELISA; (2) IgG antibody subclasses; (3) IgG and IgA avidity, (4) virus
      neutralizing functional assay; and (5) HAI antibody titer. Peripheral blood mononuclear cells
      (PBMC) isolated from these subjects will be evaluated for the following: (1) "central" and
      "effector" memory T cell responses, including their proliferative responses and cytokine
      production profiles by flow cytometry; (2) IFN-gamma production by ELISPOT, following
      specific antigenic stimulation; (3) measurement ex vivo of the frequency of circulating
      influenza-specific T cells by using commercially available MHC/tetramers and/or MHC/pentamers
      and flow cytometry; and (4) role of regulatory T cells in the modulation of influenza
      responses in the elderly. Studies for measurement ex vivo of the frequency of circulating
      influenza-specific T cells (by using commercially available MHC/tetramers and/or
      MHC/pentamers and flow cytometry) will concentrate on IFN-gamma, a cytokine shown by many
      investigators to play a central role in the host immune response to influenza antigens. If
      promising results are observed, other cytokines (e.g., IL-12, TNF-alpha) might also be
      evaluated in future investigations if sufficient cells and resources are available. Major
      factors involved in the decision to concentrate these studies on IFN-gamma include the need
      to remain focus in a defined set of scientific questions and the fact that we will only have
      access to a limited number of peripheral blood mononuclear cells (PBMCs) that might preclude
      the study of additional cytokines.
    

Time perspective: Prospective
Keywords: Fluzone; inactivated; influenza vaccine; sub-study; trivalent