Antibodies from Plants : part II
From the commercialization of the first plant-based ß-glucosidase by Protalix Bio Therapeutics for Gaucher Disease (Fox, 2012) to the recent tobacco antigens by Diamante Srl against COVID-19 (Shanmugaraj et al., 2020); plants have been used significantly to produce biopharmaceuticals and non-biopharmaceuticals (refer Table). The following case studies highlight some aspects of the ground-breaking findings of PMAbs in their different stages of development.
CASE STUDY I: ZMappTM for Ebola Virus
Ebola Virus Disease (EVD) is a deadly disease caused by Filoviridae family of viruses causing many complications such as fever, fatigue, diarrhoea and even multiorgan failure. By 2014 only few vaccines were in the pre-clinical stage hence the incidence of the West African EVD epidemic lead to one of the world’s worst health catastrophes.
Later in 2014, a seminal research by Qiu, et al. (2014) was published on ZMappTM; a triple mAb Cocktail developed using the transient expression in tobacco (Nicotiana benthamiana) for the treatment for EVD. It was developed by LeafBio, Inc., the commercial arm of MappBio (San Diego, CA, USA) and manufactured at the Kentucky Bio Processing facility (Owensboro, KY, USA); a GMP-accredited facility to reduce the risk of the 2014 outbreak giving a rapid protein response over conventional methods. A subsequent study by Zhang, et al. (2016) specifies three of the mAbs most effective against EVD — Q206, Q314, Q411.
Even though ZMappTM; is one of the best examples for a fully functional mAbs in biopharmaceutical for EVD and several studies point out that none of such countermeasures are 100% effective as the first randomized control trial for EVD by PREVAIL II Writing Group, et al. (2016) using ZMapp plusTM have not achieved statistically significant outcomes.
CASE STUDY II: anti-HIV mAbs
Human Immunodeficiency Virus Infection (HIV) caused by lentiviruses HIV-1 and HIV-2 damage the immune system resulting infections, cancers and a range of other diseases. The HIV-neutralizing mAb P2G12 was a revolutionary product by Pharma-Planta: the EU-funded academic research consortium. A recent review highlighted that Pharma-Planta’s achievement of the GMP license for innovative manufacturing procedures that resulted in the launch of the first-in-human phase I safety study of P2G12 using transgenic N. tabacum species, initiated by Ma, et al. (2015) marking a successful completion of the project.
To improve yield of existing P2G12 mAbs, Paul, et al. (2014) made an optimised variant “SIgA” using transgenic and transient tobacco leaves. Apart from P2G12, several other plant-based mAbs for HIV treatment currently available in different developmental stages. In his study Anderson, et al. (2020) describe a vaginal film “MB66” currently developed by Mapp Biopharmaceutical using tobacco plants and magnICON vectors. This antibody-based treatment consists of three humanized mAbs (VRC01,4E10, and HSV8), neutralise HIV and Herpes Simplex Viruses and recently completed a Phase 1 randomised trial (Politch, et al. 2021). A former study on plant-made VRC01 by (Hamorsky, et al. 2013) also indicated its HIV-1-neutralization capacity.
Evaluating the importance of production of more PMAbs, (Whaley, et al. 2012) highlighted the unaffordability of mammalian-cell derived mAbs particularly in underdeveloped areas, due to their high cost. “MabGel”, is one such example of a mammalian-cell based vaginal microbicide currently in its phase 1 trial (Morris, et al. 2014) with a high market price.
Over the past years, the diversity of plant antibody application has grown by leaps and bounds. As highlighted in earlier sections despite the attractiveness of plant molecular farming with respect to its conventional counterparts, regulatory barriers and the public perception towards biotechnology and GMOs hinders the adoption of recombinant PMAb production. Hence, current EU initiatives such as Pharma-Factory and Newcotiana aims to explore and resolve the bottlenecks of plant molecular farming.
Among the numerous studies explained earlier, innovative plant biotech companies like iBio Inc (Bryan, TX, USA), with their eco-friendly FastPharming® System are pioneers PMAbs production and by incorporating revolutionising techniques such as vertical farming, automatic hydroponics, and novel glycosylation they are manufacturing the next generation of biotherapeutics.
The existing strengths of plant- derived expression technologies, coupled with the upcoming innovative technologies is anticipated to accelerate the development of plant-made recombinant antibodies for the growing biotherapeutic market.
