Respiratory Syncytial virus specific immunity in hematopoietic cell transplant recipients - PROJECT SUMMARY/ABSTRACT Respiratory syncytial virus (RSV) is a common cause of lower respiratory tract infections (LRTI) in young children, the elderly and the immunocompromised. For the past year, there have been new RSV monoclonal antibodies for infants and vaccines for the elderly targeting the pre-fusion F protein, which is projected to decrease hospitalization rates due to RSV around the world. Although these preventative therapies are revolutionizing the care for immunocompetent infants and older adults, the efficacy of these therapies in immunocompromised hosts, including hematopoietic cell transplantation (HCT), recipients, is unknown, since there are no clinical trial data. With the changing landscape of RSV epidemiology, HCT recipients will remain at high risk for severe RSV disease due to increased LRTI, which is associated with 20% mortality. Sara Kim, M.D., a pediatric infectious diseases specialist at Seattle Children’s Hospital and the University of Washington, developed this career development award proposal to understand the immune parameters associated with preventing RSV LRTI in HCT recipients. Dr. Kim’s goal is to improve infectious disease outcomes in HCT recipients through better defining risk for RSV LRTI in this vulnerable population. This proposal builds upon her training in clinical infectious diseases and provides a detailed plan for career development to expand her foundations in immunology, vaccinology, biostatistics, bioinformatics, and scientific writing. To assist Dr. Kim to meet her career goals, she has assembled experts in the field of respiratory viruses in immunocompromised hosts (Drs. Waghmare and Boeckh), immunology (Drs. Catharine Bollard, Whitney Harrington, and Jim Boonyaratanakornkit), vaccinology (Drs. Janet Englund and Helen Chu) and biostatistics (Dr. Wang) whom are dedicated to ensuring the success of this project and the development of Dr. Kim’s career as an independent clinical researcher. This proposal will examine systemic and mucosal immune factors in HCT recipients with RSV infection, which provide protection against LRTI. Subaim 1a assesses humoral immunity, specifically antibodies against all RSV viral proteins using VirScan, a novel immunosurvey that utilizes phage immunoprecipitation sequencing, that are associated with prevention of LRTI. Subaim 1b will explore differences in T cell immunity in HCT recipients with RSV upper versus lower respiratory tract infections. Aim 2 of this proposal will compare mucosal and systemic antibodies against different RSV proteins using a highly sensitive and quantitative electrochemiluminescence assay and correlate with protection against LRTI. Through accomplishing the aims in this proposal, Dr. Kim will contribute significantly to understanding host immune responses in HCT recipients after natural RSV infection and provide foundations for future vaccine and therapeutics against RSV in this vulnerable population.
