Acute Radiation Syndrome: Telomere shortening as a new surrogate marker AND the Fate of Vaccine Immunity

National Institute Of Allergy And Infectious Diseases

Investigators

Abstract

This IAA is composed of 2 projects: Project 1 Hematopoietic cells and cells of the peripheral immune system are highly sensitive to the lethal effects of ionizing radiation. Treatment of the hematopoietic acute radiation syndrome (H-ARS) has largely focused on stimulating neutrophil production to protect against infection. The question of the fate of vaccine immunity, mediated by T cells, is critical as vaccine memory cannot be restored by the generation of new lymphocytes, leaving victims vulnerable to numerous exogenous and latent microorganisms to which they were previously immune. A revaccination approach involving numerous potential infectious agents may be impractical in a radiation mass casualty situation. In that light, this research will focuse on designing studies to identify a therapeutic or combination therapeutics to replace revaccination rescue. Project 2 The project will investigate telomere shortening and ARS using an immune-proficient rat model with the intent of developing telomere shortening as a surrogate marker of oxidative DNA damage due to ARS. Subsequent research will aim to translate findings from the animal model of telomere shortening using irradiated primary human tissue obtained from a repository.