Distinct antibody profiles against Ebola virus track with the development of Post-Ebola Syndrome.

Abstract Survivors of Ebola virus disease (EVD) have reported a wide range of symptoms following recovery from infection. These long-term sequelae, collectively termed post-Ebola syndrome (PES), can significantly impact the daily lives of EVD survivors, yet little is known about the underlying mechanism of PES pathogenesis. Antibodies against Ebola virus provide protection against infection through both neutralization and recruitment of innate immune effector functions via the antibody Fc region, yet persistent antibody-mediated inflammation may contribute to PES manifestations. To investigate the potential role that virus-specific antibodies have in PES, we analyzed the antibody immune profiles in a cohort of EVD survivors and household contacts that had been previously characterized for clinical sequelae. Antibodies isolated from survivors an average of 2.5 years after recovery were measured for induction of Fc-mediated innate effector function against the immunodominant antigen Ebola glycoprotein-coated targets. We found that antibodies in asymptomatic EVD survivors were qualitatively different from survivors experiencing musculoskeletal and gastrointestinal manifestations of PES. Specifically, antibodies from asymptomatic individuals induced higher levels of antibody-dependent complement deposition and monocyte-mediated phagocytosis, but not neutrophil-mediated phagocytosis, and differed in NK cell activation profiles compared with individuals with PES. Together, these data suggest that the development of qualitatively different antibodies may shape susceptibility to/protection from the development of PES and may help identify potential therapeutic targets for EVD survivors suffering from PES. Supported by Washington State University, College of Veterinary Medicine