Human Response to Influenza Vaccine Clinical Trial
Official title:
Immune Senescence in the Elderly: Comparison of Immune Responses to Influenza Vaccine In Adults of Different Ages
The immune system is central to human health and its impairment can have serious
consequences.
One of the hallmarks of aging is the progressive loss of immune function exposing older
people to increased risk from infectious diseases that would not normally be more than an
inconvenience. This project will use state-of-the-art technology developed by the Stanford
Human Immune Monitoring Center to survey older individuals for signs of immune system aging
and to gather information about the factors associated with the decline of immune function.
At the initial study visit each year, volunteers will provide information about their
current health and health history. Vital signs will be assesed and the volunteer will be
immunized with the current licensed seasonal influenza vaccine. Follow-up visits will be
conducted on Day 6-8 and Day 28, with a phone call at 6 months post-immunization. A blood
sample will be collected pre-immunization and at each follow-up visit. Volunteers will be
followed for up to 8 years.
Our main effort will be to survey elderly and younger control subject responses to influenza
vaccination using our functional cellular array technology. We will compare these results
with serum antibody responses from day 28 blood samples measuring hemagglutination
inhibition (HAI) titers against the vaccination strains. This is the accepted standard for
determining whether there is an effective antibody response to influenza vaccine antigens.
In addition, we will follow-up subjects yearly by phone to ask whether they have experienced
any influenza-like illness episodes or serious adverse events following immunization. In
this way, we will be able to correlate the accepted standard assay for an appropriate
antibody response to influenza vaccination with our new assay, and also begin what we hope
will be a valuable longitudinal study of immune responsiveness in the elderly.
We also think that there will be a T-cell array "signature" of immune senescence both in
terms of the number of responding cells and their cytokine profile that will both allow a
more rapid read-out of this condition (day 6-8 after vaccination) and give some mechanistic
clues regarding this phenomenon. In addition, we want to obtain as much information as
possible with these samples and thus propose to do the following assays:
- Subject Analysis - We will use fluorescence activated cell sorting to determine the
precise number of each white blood cell type in a given patient sample and their
activation state (B cells, T cells, NK cells, gamma-delta T cells, monocytes, dendritic
cells). We are particularly interested in whether the reports of increased CD8+CD28- T
cells or decreased gamma-delta T cells correlate with immunosenescence. This subset
analysis also will be important for normalizing the gene expression data.
- Gene Expression Analysis- We will collect part of the blood sample in a PAX gene tube
and prepare probes from the mRNA for gene expression analysis using Agilent microarrays
that survey global gene expression. This will tell us if there is a particular "gene
expression signature" that correlates with immune senescence.
- Serum Cytokine Analysis - As there have been reports of changes in the serum cytokine
repertoire in older people, we will survey serum samples for 26 different cytokines
using the Panomics/Luminex system now running the Human Immune Monitoring Center at
Stanford.
- Monocyte Activation Potential - As antigen presentation capacity may also be a variable
influencing the robustness of the adaptive immune response, in Year 1 we examined
circulating monocytes as a source of antigen presenting cells. We examined the
potential of these cells to respond to in vitro activating stimuli ( cytokines and LPS)
as measured by expression of cell surface activation markers (DR, CD86, CD40) and
intracellular phosphoproteins ( eg. pp38, pSTATs). Expression of these markers was
measured by FACS analysis.
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Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Prevention