Biomarkers of Immune Dysfunction and Vaccine Responsiveness in People with Chronic Traumatic Spinal Cord Injury
Abstract
Rationale: There are up to 2.5 million individuals estimated to be living with chronic spinal cord injury (SCI). (Chronic is typically defined as at least one from an initial traumatic injury). Despite advances in medical care over the past several decades, the life expectancy for individuals with SCI is still significantly lower than for uninjured individuals. Infections such as pneumonia are the leading cause of re-hospitalization and death for persons with SCI, who are more than 80 times more likely than uninjured individuals to die as a result of sepsis, which is a massive inflammatory response to infection that results in multiple organ failure. In addition to increased infection risk, most individuals with chronic SCI live with higher levels of inflammation in the blood, which can promote many of the medical conditions that are common in this group, such as pain, type II diabetes, and elevated risk of cardiovascular disease and stroke. Surprisingly little is known about changes in the immune system that influence infection risk or cardiovascular risk in individuals living with chronic SCI. This lack of knowledge limits the development and advancement of medicines to promote health and survival for individuals with chronic SCI . From lab experiments, we know the overall blood composition and how white blood cells behave at rest and in response to infections in healthy uninjured individuals. We and other researchers have studied some very limited aspects of this in blood samples from people living with SCI, but there is still a lot that that we still do not know or understand. In this study, we will test the hypothesis that the overall blood composition is more inflammatory and that the behavior of white blood cells at rest and in response to a flu vaccine or a COVID-19 vaccine is impaired in people living with SCI. Furthermore, we expect that the biggest changes will be measured in people with SCI who are living with most severe injuries. Objective: To test this hypothesis, in adults living with SCI compared to uninjured adults, we will determine the proportion of different types of circulating white blood cells and how they behave at rest. We will then determine how they change in response to a standard flu vaccine or the newer COVID vaccine, as well as if and how the proteins or ribonucleic acid (RNA) they make are different in quality or quantity. (RNA is the body’s genetic material that is the blueprint for making proteins.) We will also measure antibodies made after vaccination in both groups. By comparing samples collected from people with SCI who have milder or more severe injuries, we will investigate if the composition and/or behavior of WBCs correlates with the injury severity. We will also record information about how many infections a person experiences for one year, and how much exercise they routinely get, so we may determine factors in the blood or specific aspects of vaccine responses that are influenced by either infections or exercise. Study Design: We expect the study to take 3 years to perform. We will enroll 50 adults with chronic SCI, defined as having had an SCI at least 1 year before enrollment. For comparison, we will also enroll 25 uninjured adults. Each person will participate at four study visits completed during the course of 1 year. Approximately 1 tablespoon of blood will be collected at study visits, to determine the overall blood composition and to evaluate how white blood cells behave at rest, using standard lab methods. Since people with SCI are especially encouraged to get a flu vaccine every year, participants will get a flu vaccine and then have their blood drawn to test the overall blood composition, how white blood cells behave in response to the vaccine, and their antibody titers 1 month later, using standard lab methods. Given the current pandemic, we will also do the same with COVID-19 vaccine. Throughout their year of study participation, partic
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Dec 28, 2022
- Source ID
- W81XWH2211032
Entities
People
- Ona Bloom
Organizations
- The Feinstein Institute for Medical Research
- United States Army