The Immune Function Studies Core (Core C) is designed to support the proposed studies of yc Foamy Virus gene therapy for SCID-Xl that will utilize in vitro testing in cell lines as well as in vivo testing using pre- clinical animal models. The Core will support all three projects (1, 2, and 3) of this Program Project Grant and is focused primarily on evaluation of functional immune recovery after gene therapy in this severe immunodeficiency disorder. The Core will perform multi-parameter flow cytometry analyses of human, mouse, and canine cells to measure viral marking and immune reconstitution after yc FV gene therapy. In addition. Core C will evaluate restoration of specific functional deficits (for example restoration of lL-2 signaling) in yc FV treated cells and will work with the SCRl Immunology Diagnostic Laboratory (IDL) to analyze functional immune responses to neoantigen (bacteriophage OX174) vaccination in treated dogs. Flow cytometry and gene sequencing will be performed by the Core to rapidly identify affected SCID-Xl dogs shortly after birth. Core C personnel will directly assist project investigators in the analysis and interpretation of data generated by the Core. Data from these analyses will be used to evaluate which yc FV vector is most efficacious and which conditioning regimen facilitates the most complete immune recovery.

Public Health Relevance

Immune dysfunction and susceptibility to severe, life-threatening infections are the hallmarks of the fatal childhood immunodeficiency disorder, SCID-Xl. Evaluation of immune reconstitufion and recovery of functional immune responses after potentially curative gene therapy is therefore vital for judging whether a particular treatment is efficacious. Core C will evaluate immune recovery in this trial of Foamy Viral mediated gene therapy for SCID-Xl.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Program Projects (P01)
Project #
5P01AI097100-02
Application #
8567346
Study Section
Special Emphasis Panel (ZAI1-JTS-I)
Project Start
Project End
Budget Start
2013-08-01
Budget End
2014-07-31
Support Year
2
Fiscal Year
2013
Total Cost
$166,395
Indirect Cost
$27,448
Name
Seattle Children's Hospital
Department
Type
DUNS #
048682157
City
Seattle
State
WA
Country
United States
Zip Code
98105
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