Developing Vaccines for Immunological Defense from Traumatic Brain Injury
Abstract
Focus Area: Prevent: Research will address the pharmacological prevention and progression of traumatic brain injury (TBI) (Early-Career Investigator – PI) Scientific Objective, Rationale, and Focus Area: TBI often is caused by trauma to the brain, which can lead to bruising, bleeding, or other physical harm to the brain. Each year, 1.5 million people in the U.S. sustain a TBI episode, and out of the people affected, approximately 90,000 suffer from long-term disability related to TBI. Interestingly, the risk of getting a traumatic injury is highest among adolescents, young adults, and persons older than 75 years of age. Thus, the population that is most susceptible to TBI is identifiable. Also, the TBI often causes inflammation of the brain and affects the immune system. Therefore, if there was a method to train the immune system to stop or reduce the injury of the brain even before the injury occurs, it could greatly reduce the recovery time and even prevent long-term disability associated with the trauma. Currently, there is no technology that can prevent the TBI induced inflammation and therefore, this proposal is highly innovative. Moreover, this proposal will develop drugs that can be taken prior to any of the activities that can lead to trauma of the brain. Therefore, the ultimate application of the research will be to develop vaccines for TBI. This project directly addresses the focus area of approaches or tools to prevent or mitigate brain injuries or psychological health conditions and assess health status. Within this section, more specifically, this proposal addresses Development of innovative materials and technologies that can prevent or mitigate TBI. Overview of Proposed Research: The main objective of this proposal is to develop vaccines for preventing the damage caused by trauma associated with inflammation. The hypothesis of this project is that vaccines will be designed that can teach the immune cells that are specific to the brain to suppress the immune system responses that lead to tissue damage. This hypothesis is based on the data that we have obtained, which preliminarily show that it is possible to generate a vaccine that can modify the function of immune cells in the periphery. The projects in this proposal will look at the immune cells in the brain itself. Specifically, this proposal is divided into two milestones namely: Milestone 1. Develop vaccines and evaluate their ability to generate memory TBI-specific immune system suppressive cells called Tregs (duration of the project: months 0–12). In this milestone, vaccines will be generated that can generate different types of immune system suppressive cells. These cells will be analyzed and will be ready to infiltrate the brain if there are any injuries to prevent further tissue damage. Milestone 2. Develop vaccines that prevent the inflammation in the brain after TBI in mice (duration of the project: months 6–24). In this milestone, the ability of the vaccines formulations to reduce inflammation in the brain will be studied in a long-term mouse model. The results from this study will determine whether the vaccines can prevent long-term inflammation in mice. Applicability and Impact of the Research to Service Members, Veterans, Military Beneficiaries, and/or the American Public: The results from this project will have a direct impact on military personnel, Veterans, and American public because of the development of vaccines that will accelerate regeneration and prevent further trauma to the brain. Service Members, Veterans, and Military Beneficiaries. Among returning Service Members, approximately 15.2% to 22.8% suffer from mild to moderate TBI, ultimately affecting as many as >400,000 troops. Moreover, due to TBI, the Veterans often suffer in higher numbers from related diseases. Therefore, addressing this issue even before the TBI occurs is very important to prevent chronic inflammation and related
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Dec 28, 2022
- Source ID
- W81XWH2210388
Entities
People
- Abhinav Acharya
Organizations
- Arizona State University
- United States Army