Characterizing Immunologic Predictive Factors of Enterovirus D68 (EV-D68) Disease Presentations in Acutely Exposed and Infected Individuals

PROJECT SUMMARY (ABSTRACT): Enterovirus D68 (EV-D68) is a non-polio enterovirus that primarily causes respiratory illness, particularly in children. While many individuals infected with EV-D68 may have mild symptoms, others have more severe presentations including severe asthma-like respiratory illness requiring intensive care and acute flaccid myelitis (AFM) that can lead to permanent polio-like paralysis. Large outbreaks of EV-D68 and increases in AFM cases have occurred in cyclic patterns since 2014. However, no effective treatments or vaccines against EV-D68 are available. Challenges to the development of such tools include gaps in knowledge about the immune response to respiratory viruses such as EV-D68. Passive transfer of EV-D68 antibodies provides protection against EV-D68 infection and severe disease in animal models; however, the role of humoral immunity in humans acutely exposed to or infected with EV-D68 is unknown. Understanding the role of the human humoral immune response in the development of different disease presentations of EV- D68 infection is essential to inform the development of effective therapeutic and preventative tools. In this study, the candidate proposes to investigate clinical factors and the role of humoral immunity as a predictor of EV-D68 infection and disease. Through the analysis of previously and prospectively collected de- identified clinical data and biospecimens from cohorts of individuals with acute EV-D68 infection or exposure, the candidate will address the research aims of: 1) describing the clinical spectrum and identifying clinical factors predictive of different EV-D68 disease presentations and 2) characterizing the humoral immune response to EV-D68 by evaluating the dynamics of the humoral immune response and identifying immunologic predictive factors of disease presentations of EV-D68 infection in humans. This study will improve the understanding of the role the humoral immune response to EV-D68 exposure and infection has to development of disease which will inform immune correlates of protection to guide development of potential monoclonal antibody treatments and next-generation vaccine candidates. The candidate is committed to a career in research in emerging infectious diseases such as EV-D68 in which she has both clinical and research experience with children with EV-D68 infection. The objective of this career development award is for the candidate to enhance skills in patient-oriented clinical research to become a successful independent investigator. Through didactic coursework in pursuit of a PhD, experiential training, and seminars/workshops she will build on her knowledge and skillset in areas of team science, clinical research, biostatistical analysis, and clinical outcomes. The guidance of her multidisciplinary mentorship team and advisors who have expertise in EV-D68 and AFM, immunology, and clinical research, will ensure the candidate successfully achieves her goals and aims in the proposed study.