Immune Memory

  • Goronzy, Jorg (PI)
  • Kinney, Lea (PI)
  • Kinney, Lea (PI)
  • Kinney, Lea (PI)
  • Kinney, Lea (PI)
  • Kinney, Lea (PI)
  • Kinney, Lea (PI)
  • Kinney, Lea (PI)
  • Kinney, Lea (PI)
  • Kinney, Lea (PI)
  • Kinney, Lea (PI)
  • Kinney, Lea (PI)
  • Kinney, Lea (PI)
  • Kinney, Lea (PI)
  • Kinney, Lea (PI)
  • Kinney, Lea (PI)
  • Kinney, Lea (PI)
  • Kinney, Lea (PI)

Project: Research project

Project Details

Description

Our goal is to understand how a successful vaccine induces long-term immunological memory and protective
immunity in humans. To achieve this goal we have initiated a detailed cellular and molecular characterization
of human immune responses induced by the yellow fever virus (YFV-17D) vaccine. This is one of our most
efficacious vaccines and induces long-term immunity that lasts for decades. Also, since YFV-17D is a live
attenuated vaccine and most of the U.S. population is not exposed to YFV-, this provides a unique
opportunity to analyze antiviral responses in humans during the course of a primary infection and then to
monitor the generation and maintenance of immune memory after resolution of the infection. One of the
potential benefits of understanding how a successful vaccine induces long-term protective immunity is that
this knowledge can be applied to improving other less effective vaccines and, more importantly, to develop
new vaccines against emerging diseases. During the previous cycle of funding we have made substantial
progress in characterizing human memory T and B cell responses not only to YFV but also after
immunization with small pox and influenza vaccines. In this renewal application we will focus our studies on
CDS T cells and examine the mechanisms that regulate human effector and memory CDS T cell
differentiation. The following specific aims are proposed to achieve our goals: 1) To identify transcription
factors that regulate naive to effector CDS Tee// differentiation. 2) To analyze the in vivo turnover of human
YFV specific CDS T cells and to examine their homing potential. 3) To define the genomic and epigenetic
changes that occur during human memory CDS T cell differentiation.These studies will will provide the first
view of the transcriptional changes that occur following CDS T cell differentiation in humans and will provide
unique markers that will enable identification, isolation, and characterization of the differentiated cell subsets.
Examination of the epigenetic DMA methylation marks during the progression of the T cell response, as well
as between CD8 T cells responding to acute versus chronic viral infections will provide a potential
mechanistic view of how memory CDS T cell differentiation is globally regulated.

StatusNot started

Funding

  • National Institute of Allergy and Infectious Diseases

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