In its monthly webinar series, the DOST-Biosafety Committee (DOST-BC) invited two highly respected individuals in the field of Plant Biotechnology, Dr. Julian Ma and Dr. Stefan Schillberg last May 22, 2021 via Zoom platform.
Dr. Julian Ma is the Hotung Chair of Molecular Immunology and Director of the Institute for Infection and Immunity at St. Georges, University of London. Dr. Ma’s research group studies basic mechanisms of protein assembly, processing and expression in plant cells, as well as the design, engineering and clinical applications of novel recombinant proteins in plants for systemic and mucosal vaccination and immunotherapy. His work focuses on infectious diseases that predominantly affect the poor in developing countries, including HIV, rabies, chikungunya, dengue, Ebola and TB. Dr. Ma is a leading proponent in Europe for the development of plant biotechnology for medicines for human health and has led several major European research consortia, notably performing the first ever clinical safety trial in humans of an HIV antibody produced in tobacco plants.
In Dr. Ma’s presentation on Molecular Pharming of Plant-Produced Biologics, he underscored the following beneficial points in Molecular Pharming:
- It offers a suite of manufacturing technologies
- Low-cost early investment
- Large Scale Production
- Established transgenic and transient expression platforms
- Developed regulatory pathways
- Speed of delivery for rapid response biologics
- A source for multi-component products for difficult vaccines, or cancer treatment
- Alternatives to antibiotics
- Multimeric complexes with enhanced biological activity
Dr. Ma explained that plants are excellent expression system for virus-like particles (VLP) vaccine candidates like Hepatitis B (core), Norwalk virus (capsid), Bluetongue (multimer), Cowpea mosaic (multimer), Human papillomavirus 8 (L1), Bovine papillomavirus (L1), Influenza (HA), Rotavirus (VP2, VP4, VP6, VP7), Polio and SARS-CoV-2
Dr Ma also gave examples of commercial developments in molecular pharming such as the Protalix Biotherapeutics Inc. which received commercial license for Elylyso by Pfizer in 2012. Elylyso is an injection for the treatment of patients with a confirmed diagnosis of Type 1 Gaucher disease.
Other products developed by the National Institute of Advanced Industrial Science and Technology (AIST) of Japan and BioApp of Korea is for use in veterinary medicine such as “Interberry alpha” for gum disease in dogs and the “Herbavac CSF Green Marker”, a plant-derived recombinant subunit vaccine against Classical Swine fever virus. Other interesting products from molecular pharming is for production of cosmetic products such as the Bioeffect EGF Cellular Activating Serum, an anti-aging serum from Iceland and ISTINA from Natural Biomaterial Inc. of Korea which were given fast regulatory approvals.
Dr Ma emphasized that there are easy ways to produced medicine in the market, however, it must establish the facilities first, and demonstrate the capability to manufacture under certain safety conditions. These however, will be subject to more strict scrutiny under the pharmaceutical route.
With the continuous growth of Molecular Pharming, Dr. Ma showed some molecular pharming facilities around the world for the following diseases:
- Flu vaccines
- Yellow fever vaccine
- Gum disease
There is clearly an emerging interest on the next generation biologics using monoclonal antibodies to treat infections or cancer and the development of vaccines in human. The team of Dr. Ma did an early clinical trial on the monoclonal antibodies produced in tobacco to prevent tooth decay. Another project is a European consortium which includes Dr. Ma and Dr. Schillberg’s group which developed a monoclonal antibody against HIV which is already into Phase I clinical trial which was already granted approval by the regulatory arm of the United Kingdom (UK).
Plant Biotechnology against COVID
In the second presentation, Dr. Schillberg presented the application of plant biotechnology in the fight against SARS-CoV-2 (Corona Virus).
Dr, Schillberg is a member of the Institute Management and Head of the Division of Molecular Biotechnology at the Fraunhofer Institute for Molecular Biology and Applied Ecology IME in Aachen, Germany. He has more than 25 years’ experience in biotechnology with a major focus on the production of recombinant proteins in various hosts including plants and plant suspension cells, metabolic pathways engineering, genome editing, strategies to scale-up processes and to improve product levels in plants as well as engineering novel traits in crops.
He started his presentation with a brief summary of the benefits and unique features of Molecular Pharming. He then discussed the production of diagnostic reagents, vaccine candidates and antiviral proteins where tobacco plant is being used as the main source. Dr. Schillberg also underscored the value of tobacco plant, not just for virus detection but also for developing a vaccine that could mitigate the severity of the virus. The procedure is to create anti-bodies to fight the virus and to do a preclinical vaccine studies to ensure that the developed vaccines would work.
He also mentioned that all these clinical trails are mainly done through animals to measure the efficacy and safety before going through human clinical trial.
Dr. Schillberg further discussed about the plant-made SAR-CoV-2 diagnostic proteins wherein he elaborated that there is already a proof of concept study of a plant-based production process for the virus on Spike S1 protein. This process can rapidly scale the production in just 12 weeks, which is said to be vital in facing a pandemic.
He then elaborated on the following processes:
- Transient protein expression in Nicotiana benthamiana plants
- Process steps of the proof of concept study
- Rapid detection of SARS-CoV-2 specific antibodies
In the end, both Dr. Ma and Dr. Schillberg agreed that these kinds of development can be a game-changer in early diagnostics where we can obtain cheaper yet efficient vaccines with a faster pace of production. #