Anti-Ebola therapies based on monoclonal antibodies: current state and challenges ahead

Abstract

The 2014 Ebola outbreak, the largest recorded, took us largely unprepared, with no available vaccine or specific treatment. In this context, the World Health Organization (WHO) declared that the humanitarian use of experimental therapies against Ebola Virus (EBOV) is ethical. In particular, an experimental treatment consisting of a cocktail of three monoclonal antibodies (mAbs) produced in tobacco plants and specifically directed to the Ebola virus glycoprotein (GP) was tested in humans, apparently with good results. Several mAbs with high affinity to the GP have been described. This review discusses our current knowledge on this topic. Particular emphasis is devoted to those mAbs that have been assayed in animal models or humans as possible therapies against Ebola. Engineering aspects and challenges for the production of anti-Ebola mAbs are also briefly discussed; current platforms for the design and production of full-length mAbs are cumbersome and costly.

Monoclonal antibodies for the treatment of Ebola virus disease

“…Pointing out that with the current technique to produce MAbs from transfected tobacco plants; in order to produce, as an example, 50 kg of MAbs to allow for the treatment of maybe 5000 individuals, the authors calculate that 150 tons of tobacco leaves would have to be transfected. This is a dimension exceeding current facilities by far; apart from the fact that the MAbs recovery process from tobacco biomass poses its own formidable technical challenges [30].…”

“…As comprehensively reviewed recently by Gonzalez-Gonzalez et al [30]; up to date, around 20 monoclonal antibodies have been identified and characterized, of which some were found promising to progress to testing in nonhuman primate models. This included KZ52, isolated from a human survivor and successful in protecting mice and guinea pigs from lethal infection, but failing to protect NHPs when administered as single antibody [13].…”

“…The light chain of the IgG molecule is made up of two domains, whereas the heavy chain contains four [37]. Murin et al [13] describe the specific structure of EVDprotective antibodies in detail and discuss them in relation to the specificities of the GP target; González-González et al summarize the up-to-date knowledge on the structure and mode of action of mABs as well as the structure of the targeted Ebola virus GP [30].…”

“…González-González et al [30] thoroughly examined the currently available and potential future techniques and highlight that firstly, MAbs required for successful treatment attempts may amount to as much as 10 g/patient; and that within a massive outbreak situation, MAbs needs may rapidly run up to many kilograms. Pointing out that with the current technique to produce MAbs from transfected tobacco plants; in order to produce, as an example, 50 kg of MAbs to allow for the treatment of maybe 5000 individuals, the authors calculate that 150 tons of tobacco leaves would have to be transfected.…”

“…A future option to be still thoroughly researched could be engineered mAb fragments in place of full-length MAbs, which could make it probably more easily into mass production [30].…”