Associations Between Antibody Fc-Mediated Effector Functions and Long-Term Sequelae in Ebola Virus Survivors

Abstract

Antibodies that mediate non-neutralizing functions play an important role in the immune response to Ebola virus (EBOV) and are thought to impact disease outcome. EBOV has also been associated with long term sequelae in survivors, however, the extent to which antibodies that mediate non-neutralizing functions are associated with the development of these sequelae is unknown. Here, the presence of antibodies mediating different effector functions and how they relate to long-term sequelae two years after the 2007 Bundibugyo Ebola virus (BDBV) outbreak was investigated. The majority of survivors demonstrated robust antibody effector functional activity and demonstrated persistent polyfunctional antibody profiles to the EBOV glycoprotein (GP) two years after infection. These functions were strongly associated with the levels of GP-specific IgG1. The odds of developing hearing loss, one of the more common sequelae to BDBV was reduced when antibodies mediating antibody dependent cellular phagocytosis (ADCP), antibody dependent complement deposition (ADCD), or activating NK cells (ADNKA) were observed. In addition, hearing loss was associated with increased levels of several pro-inflammatory cytokines and levels of these pro-inflammatory cytokines were associated with lower ADCP. These results are indicating that a skewed antibody profile and persistent inflammation may contribute to long term outcome in survivors of BDBV infection

Antiviral and clinical activity of bamlanivimab in a randomized trial of non-hospitalized adults with COVID-19

“…Considering the different mechanisms of action and half-life of bamlanivimab and molnupiravir, these data suggest the initial improvement in inflammatory markers is due to direct virus neutralization and inhibition of further viral replication. However, one could consider if there might be further benefit specific to mAbs that is not related to direct antiviral activity, such as through non-neutralizing Fc-mediated effector functions 18 and clearance of infected cells, that could theoretically induce greater and more prolonged benefits in SARS-CoV-2-associated inflammation and complications; a head-to-head study of small molecule antivirals with antibody-based therapies would be needed to explore this. As more potent oral antivirals for COVID-19 are becoming increasingly available, future studies are needed to interrogate the potential benefits of small molecule vs antibody-based antivirals for populations at high risk of severe COVID-19 (immunocompromised persons with limited endogenous immune responses) and for potential inflammation-mediated complications in all persons at risk for COVID-19, such as post-acute sequelae of SARS-CoV-2 infection (PASC).…”

FcγR Genetic Variation and HIV-1 Vaccine Efficacy: Context And Considerations

“…severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) ( 73 )], and emerging/re-emerging infectious diseases [e.g. Ebola ( 74 , 75 )].…”

ALVAC-HIV and AIDSVAX B/E vaccination induce improved immune responses compared with AIDSVAX B/E vaccination alone

“…Antibody avidity was determined by surface plasmon resonance using a Biacore 4000 as previously described ( 18 , 19 ). Innate effector function assays, including ADCC, ADCP, ADNP, ADCD, trogocytosis, and NK cell activation were performed as previously described ( 20 , 21 ). Detailed methods for immunoassays are available in the supplemental material.…”