Monoclonal antibodies for the treatment of Ebola virus disease

Abstract

Introduction: To date, the management of patients with suspected or confirmed Ebolavirus disease (EVD) depends on quarantine, symptomatic management and supportive care, as there are no approved vaccines or treatments available for human use. However, accelerated by the recent large outbreak in West Africa, significant progress has been made towards vaccine development but also towards specific treatment with convalescent plasma and monoclonal antibodies. Areas covered: We describe recent developments in monoclonal antibody treatment for EVD, encompassing mAb114 and the MB-003, ZMAb, ZMapp ™ and MIL-77E cocktails.Expert opinion: Preventive measures, are, and will remain essential to curb EVD outbreaks; even more so with vaccine development progressing. However, research for treatment options must not be neglected. Small-scale animal and individual human case studies show that monoclonal antibodies (mAbs) can be effective for EVD treatment; thus justifying exploration in clinical trials. Potential limitations are that high doses may be needed to yield clinical efficacy; epitope mutations might reduce efficacy; and constant evolution of (outbreak-specific) mAb mixtures might be required. Interim advice based on the clinical experience to date is that treatment of patients with mAbs is sensible, provided those could be made available in the necessary amounts in time.ARTICLE HISTORY

Why are vaccines against many human viral diseases still unavailable; an historic perspective?

“…The mAb, Palivizumab, has been licensed for clinical use in the prevention of RSV infection. Combinations of up to three therapeutic mAbs have also been considered for development as a possible PIT in Ebola virus infections . A related development in the use of postexposure prophylaxis, involves the use of combination passive and active immunization which is widely used for the treatment of verified rabies infections…”

“…Combinations of up to three therapeutic mAbs have also been considered for development as a possible PIT in Ebola virus infections. 19,20 A related development in the use of postexposure prophylaxis, involves the use of combination passive and active immunization which is widely used for the treatment of verified rabies infections. 21 It has become apparent that anticancer antibodies act, at least in part, by harnessing effector responses of the innate immune system (antibody-dependent cell-mediated cytotoxicity (ADCC) and antibody-dependent cell-mediated phagocytosis (ADCP) or complement activation.…”

Viral glycoproteomes: technologies for characterization and outlook for vaccine design

“…The 2014 Ebola virus outbreaks in West Africa lead to cooperation between public and private organizations and development of a vaccine in under a year . Furthermore, several monoclonal antibody cocktails were developed for disease treatment . Ebola virus envelope glycoprotein is heavily glycosylated with both N‐ and O‐linked glycans .…”

Filovirus – Auslöser von hämorrhagischem Fieber

“…Die Wirkung von Rekonvaleszentenplasma ist vom EBOV-GP IgG-Titer abhängig [143]. Eine Übersicht zur Herstellung und Wirkung von monoklonalen Antikörpern und Rekonvaleszentenplasma findet sich bei Moekotte et al [144] und Rojek et al [145]. Der wirkliche Nutzen von Rekonvaleszentenplasma bleibt zurzeit unklar, da die Präparate wegen der abflauenden Epidemie nur an einzelnen Patienten getestet werden konnten [95,146,147].…”