We will use cutting edge single T cell analysis techniques to molecularly define the T cell repertoire and function of cellular immune responses of individuals 65 years of age or older. The mechanisms behind declining immune responses with age is likely multifactorial. Aging is associated with a reduction in the frequency of antibody secreting cells and the number of lymph node germinal centers, and we hypothesize this to be due to impaired ability of CD4+ T cells to provide adequate help to B cells. T follicular helper cells in germinal centers directly provide help to B cells, and induce them to become antibody-secreting plasma cells. We have previously demonstrated the frequencies of activated peripheral T follicular helper cells (pTfh) and circulating plasmablasts shortly after vaccination is directly related to subsequent titers of vaccine-specific antibodies. Furthermore, high dose influenza vaccine (IIV HD) was better able to induce activated pTfh cells than standard dose vaccine (IIV SD). In this application we will probe the mechanisms behind successful immune responses to vaccines in an elderly population. We will evaluate the immune T cell repertoire, the transcriptomic profile of responding cells, and inflation of CMV-reactive T cells in elderly individuals and determine the effect of these factors on the host's ability to mount successful immune responses to vaccines. !

Public Health Relevance

In this project we will investigate immunological factors that predict the degree to which elderly individuals are able to respond to influenza vaccines. We will specifically determine whether limited T cell receptor repertoires, and/or decreased functional T cell responses diminish vaccine responses in this group.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
5R01AI142095-02
Application #
9882207
Study Section
Special Emphasis Panel (ZAI1)
Program Officer
Prabhudas, Mercy R
Project Start
2019-03-01
Project End
2024-02-29
Budget Start
2020-03-01
Budget End
2021-02-28
Support Year
2
Fiscal Year
2020
Total Cost
Indirect Cost
Name
Vanderbilt University Medical Center
Department
Type
DUNS #
079917897
City
Nashville
State
TN
Country
United States
Zip Code
37232