Rescue of vaccine immunity with nicotine and isoproterenol after total body irradiation

• Published in: The Journal of immunology (1950) Vol. 200; no. 1_Supplement; pp. 125 - 125.27
• Main Authors: Gandhi, Deep, Lehtimaki, Mari K., Surujdin, Ryan, Aryankalyil, Joseph, McFarland, Hugh I., Rosenberg, Amy S.
• Format: Journal Article
• Language: English
• Published: 01-05-2018
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.200.Supp.125.27

Radiation exposure results in DNA damage and apoptosis of lymphocytes, including memory T cells, leading to the loss of vaccine immunity and resulting in a potentially lethal susceptibility to infection. We have shown that memory CD8+ T cells are preserved by revaccination within 3–4 days after exposure to sub-lethal γ radiation. This study explores therapeutics selected to replicate the effects of revaccination. These therapeutics may promote memory T cell survival by acting on survival pathways stimulated by T cell activation. Using a Listeria monocytogenes (LM) model in mice, nicotine tartrate and isoproterenol were chosen from a screen of 22 therapeutic candidates. Both drugs have been shown to act on the AKT and ERK1/2 survival pathways to prevent apoptosis and promote cell survival and DNA repair. Thirty days after vaccination against LM, mice were irradiated and treated 1 day later with one of the therapeutics. Thirty days later, mice were challenged with wild-type LM, followed by harvest and plating of the spleen. Colonies were counted as a measure of vaccine immunity to LM. Nicotine significantly decreased the number of LM colonies when administered subcutaneously in a TiterMax adjuvant emulsion, as well as transdermally in the form of a patch. The decrease in LM was comparable to revaccination. Similarly, pilot experiments using isoproterenol show decreased colony counts, indicating potential preservation of vaccine immunity. Further studies will include varying doses of isoproterenol and varying routes of administration, as well as combinations of treatments. These therapeutics offer a practical effective means of preserving vaccine memory as a potential new medical countermeasure for Acute Radiation Syndrome.