Graduate Student University of Illinois, Chicago Rockford, Illinois, United States
Disclosure(s):
Rashmitha Vedasistla, MS: No financial relationships to disclose
Introduction/Rationale: Amyotrophic Lateral Sclerosis (ALS) is a progressive neurodegenerative disease that causes muscle paralysis and death within 2–5 years of diagnosis. Currently, there is no effective treatment. Emerging research suggests that regulatory T cells (Tregs) play a neuroprotective role in ALS; however, pathogenic antigens in ALS remain unknown, hindering the development of strategies to expand disease relevant Tregs. Recently, we developed an antigen less pro vaccines (ALPV) that can form an active vaccine in situ with endogenous pathogenic antigens overexpressed at disease sites. Here, we aim to explore this novel vaccine in an ALS mouse model.
Methods: To enable straightforward tracking and quantification of Tregs, a substrain of ALS prone mice was generated by crossing Foxp3 eGFP/Ki67 tagRFP mice with SOD1 G93A mice. Beginning at 12 weeks of age, mice were treated with ALPV; PBS injected mice served as controls. At defined time points post treatment, circulating Tregs were quantified via immunostaining and flow cytometry.
Results: Our results showed that ALPV treatment increased Treg levels approximately fivefold, with additional significant spinal cord data supporting this expansion. Next, behavioral studies will be conducted to determine whether ALPV can delay disease progression.
Conclusion: Our finding that ALPV significantly expands Tregs in treated mice highlights its promise as a novel treatment for ALS. Critically, by bypassing the need for an exogenous immunogen, ALPV may serve as a universal vaccine for other neuroinflammatory diseases, even in cases where pathogenic autoantigens remain unknown.
