RT Journal Article
SR Electronic
T1 Development of therapeutics to maintain vaccine immunity following exposure to ionizing radiation.
JF The Journal of Immunology
JO J. Immunol.
FD American Association of Immunologists
SP 79.30
OP 79.30
VO 198
IS 1 Supplement
A1 McFarland, Hugh I
A1 Surujdin, Ryan T
A1 Aryankalayil, Joseph
A1 Berkson, Julia D.
A1 Lee, Jay P.
A1 Rosenberg, Amy S.
YR 2017
UL http://www.jimmunol.org/content/198/1_Supplement/79.30.abstract
AB Exposure to γ radiation from nuclear power plant disasters, terrorist acts, and medical procedures devastate the peripheral immune system, killing both naïve and memory T cells. Although, naïve T cells recover, memory T cells mediating vaccine immunity are permanently lost rendering a victim highly susceptible to infection. There is no treatment to globally preserve vaccine immunity following ionizing radiation exposure. We have recently published that CD8+ memory T cell responses to Listeria can be preserved in the aftermath of radiation exposure by revaccination within 3–4 days after irradiation. A correlation between survival and T cell activation prior to irradiation has been demonstrated in vitro. Comprehensive revaccination in a radiation mass casualty situation would be problematic from many perspectives. We are working to develop a therapeutic regimen to replicate the pro-survival effects of revaccination. Among the signaling pathways stimulated by T cell activation is the Akt “survival pathway” which inhibits apoptosis, and enhances the rate and fidelity of repair of damaged DNA. Agonists or inhibitors targeting the various receptors and signaling molecules that interact within this pathway may result in survival of memory T cells and are potential therapeutic candidates. In addition, revaccination rescue upregulates p21 mRNA. p21 is strongly anti-apoptotic, and enhances DNA strand break repair. In preliminary studies, a number of candidate therapeutics have been identified including nicotine, which virtually eliminates splenic Listeria in immunized and irradiated mice following challenge with wild-type bacteria. Testing is underway with nicotine patches which would provide an ideal method of administration.