Tolerogenic Vaccine for Control and Recovery in Traumatic Brain Injury

Abstract

Traumatic brain injury (TBI) is a leading cause of morbidity and mortality worldwide. While many safety interventions have been implemented to reduce occurrence, the options to treat TBI post injury are severely lacking. In order to address this need, this project presents preclinical evidence on the use of tolerogenic vaccines to reduce neuro inflammation and promote tissue regeneration. Previous work has shown the ability for polymeric alpha-ketoglutarate (paKG) in combination with PFK15 (a small molecule glycolytic inhibitor) to modulate metabolic activity in dendritic cells (DC) leading to preferential presentation of antigens to immunosuppressive Tregs. Using this method in combination with neuro specific auto antigens PLP and MOG; a vaccine can be made that attenuates inflammation and promotes tissue regeneration in a TBI mouse model. C57BL/6J mice were treated prior to injury and brains were collected at days 28 and 60 for histology analysis. Brain segments were stained for CD86, GFAP, Iba1 and DAPI. Image analysis was performed to measure injury area and fluorescence expression. Results from this study showed a significant decrease in CD86+ DC expression in the ipsilateral cortex in the full treatment group compared to a negative saline control (P=.0159). However, no significant difference was seen in injury area or GFAP or Iba1 expression suggesting limited effect on neural tissue outcomes. This result shows promise for tolerogenic vaccines in TBI and underscores the importance of optimizing the vaccine treatment protocol to achieve lasting improvements to neural tissue health.

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