Immune Genomics and COVID-19 Vaccine Response in Adults with Adverse Childhood Experiences
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Principal Investigator: Bart Nolan Ford Organization: OSU CENTER FOR HEALTH SCIENCES Fiscal Year: 2022 Award: $133,636 Funding agency: National Institute of General Medical Sciences Abstract The lifelong influence of adversity during development on gene regulation in the immune system offers insight into COVID-19 related health disparities. However, the pathways by which adverse childhood experiences (ACEs) disrupt immune function throughout life are not fully understood and it is unknown how ACEs may influence COVID-19 vaccine immune response. The conserved transcriptional response to adversity (CTRA) is a gene expression pattern characterized by up-regulated inflammatory and down-regulated type I interferon (IFN) anti-viral genes. The CTRA has been recognized across many studies of adverse social conditions including in young adult and adolescent survivors of trauma. COVID-19 vaccine protection relies upon appropriate inflammatory and IFN responses by antigen presenting cells (APCs) to initiate lasting immune memory. Two types of APCs, monocytes and dendritic cells (DCs) have been bioinformatically identified as primary cell types affected by the CTRA, though direct measurement of gene expression in both cell types has not been performed. This project will recruit a sample of COVID-19 vaccinated adults with no known prior SARS-COV-2 infection. The CTRA will be quantified in isolated monocytes and DCs using RNA sequencing and vaccine response will be determined by circulating antibody concentration and T-cell response in functional assays. We expect that ACEs will be negatively associated with COVID-19 vaccine response, positively associated with CTRA associated inflammatory gene expression in monocytes, and negatively associated with CTRA associated type I IFN gene expression in DCs. Because DCs play a central role in the activation of T-cells and antibody producing B-cells following vaccination, we expect that antiviral gene expression will be positively correlated with COVID- 19 vaccine antibody and T-cell immunity. This innovative study will elucidate a biological pathway by which ACEs diminish function of the immune system through molecular deviations in specific cell types. Although the current vaccines are highly effective at preventing severe COVID-19, the degree of variability in the initial immune response may influence the longevity of immune protection. Thus, our findings may have implications for differential booster vaccine recommendations according to history of ACEs. 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